©1991S Karger A G , Basel 0028-2766/91/0571-0040S2.75/0
Nephron 1991;57:40-44
Renal Replacement Therapy in Autosomal Dominant Polycystic Kidney Disease Satwant Singh. Sundaram Hariharan University of Cincinnati Medical Center, Dialysis Clinic Inc. and Veterans Administration Medical Center, Cincinnati, Ohio, USA
Keywords. Autosomal dominant polycystic kidney disease • Renal replacement therapy • Morbidity • Mortality • Hemodialysis • Peritoneal dialysis • Renal transplantation Abstract. Autosomal dominant polycystic kidney disease (ADPKD) accounted for 4.6% of our end-stage renal disease (ESRD) population. Initial ESRD therapy consisted of hemodialysis in 78% and continuous ambulatory peritoneal dialysis in 22% with significant intertherapy transfers. Half of these patients underwent one or more renal transplantations. Infections, primarily related to ADPKD or ESRD therapy, were the leading cause of morbidity in these patients. 3% of total time on ESRD therapy was spent in hospital, half of it due to problems related to ADPKD and ESRD therapy. Overall mortality and morbidity (as measured by hospitalization rates) in ADPK D patients were similar to those in a non diabetic ESRD population.
Autosomal dominant polycystic kidney disease (ADPKD) is an important cause of end-stage renal dis ease (ESRD) accounting for 2-9% of this population worldwide [1]. The paucity of information about the clini cal characteristics of ADPKD patients with ESRD prompted us to analyze our data in 60 such patients. The objective of this study was to assess morbidity and mor tality in this population and compare these to those in a nondiabetic ESRD population.
Patients and Methods The diagnosis of ADPKD was made at or before the onset of ESRD therapy by history, physical examination and radiological studies such as intravenous pyelography, ultrasonography and/or computed tomographic scan. The study cases were drawn from patients who received some form of renal replacement therapy at the University of Cincinnati Medical Center (UCMC), Dialysis Clinic Inc. (DCI) or Veterans Administration Medical Center (VAMC), Cincinnati, betweeen January 1973 and December 1987. A compu terized data base developed at the UCMC Division of Nephrology [2] has been used for day-to-day management and record keeping of ESRD patients. The clinical characteristics of these patients were analyzed retrospectively from the computer data bank, aided by
chart review where indicated. The Cox proportional hazard model [3] was used to assess the influence of various factors, including ADPKD, on survival in those ESRD patients who were started on renal replacement therapy at UCMC. The morbidity and mortality in the ADPKD population were compared with those in nondia betic ESRD patients.
Results Among a total of 1,172 patients there were 54 patients (4.6%), 32 males and 22 females, with ADPKD who received renal replacement therapy between 1973 and 1987 at UCMC and DCI. In addition, there were 6 ESRD patients with ADPKD at VAMC. Thus, a total of 60 ESRD patients with ADPKD were available for analysis. The mean age at the start of ESRD treatment in these patients was 47.3 ± 15.2 years (SD). There were 51 whites, 8 blacks and I Asian followed for 1-204 months (mean 59.7 months). The average time between the diagnosis of ADPKD and the start of ESRD treatment was 8.85 ± 3.2 years. Renal replacement therapy consisted of hemodialysis, continuous ambulatory peritoneal dialysis (CAPD) and renal transplantation. A total of 47 (78%) patients were started on hemodialysis as the initial mode of renal re-
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Introduction
41
ESRDTherapy in ADPKD
Tabic 1. Systemic diseases in ADPKD patients diagnosed after initiation of renal replacement therapy Category
Patients n
Infections Related to ADPKD/ESRD therapy Not related to ADPKD/ESRD therapy Gastrointestinal diseases Cardiovascular diseases Pulmonary diseases Neoplastic diseases Others Total
68 55 13 42 28 13 10 11 172
% 40
24 16 8 6 6 100
Table 2. Hospitalization data in ADPKD patients on ESRD therapy 107,460 Total days at risk 320 Total number of hospitalizations Average stay per hospitalization, days 10.2 10.9 Inpatient days/patient/year 3,264 Total inpatient days Total inpatient days as percent of total days at risk 3 1,642 (50%) Inpatient days related to ESRD therapy 1,152 (35%) Related to dialysis Related to transplant 491 (15%) 1,621 (50%) Inpatient days not related to ESRD therapy
Table 3. Surgical intervention in ADPKD patients while on ESRD treatment S u rg e ry re la te d to A D P K D /E S R D
Vascular access Peritoneal access lransplantation Pretransplantation nephrectomy/splenectomy Parathyroidectomy Total
68 20 32 18 4 142
S u rg e ry n o t re la te d to A D P K D /E S R D
Hernia repair, urethral dilatation Occular lens extraction, colectomy, prostatectomy, hystercctomy-oopherectomy Vagotomy-pyloroplasty, pneumonectomy Others Total
5 each
Grand total
174
3 each 2 each 6 32
34 infectious episodes occurred in 30 immunosuppressed transplant patients (18 bacterial, 14 viral and 2 fungal). 3 of these proved fatal (2 fulminant cytomegalo virus infections and 1 Gram-negative septicemia). While infectious events occurred equally amongst the trans plant and dialysis patients (34 episodes in each group), infections were responsible for more deaths in the dialy sis group as compared to the transplanted group (7 vs. 3). Gastrointestinal problems were diagnosed frequently after the onset of ESRD. Peptic ulcer disease was the most common (14 patients) followed by hiatal hernia (11) and colonic diverticular disease (8), cholelithiasis (4), pancreatitis (3) and cholecystitis (2). The next most com mon system involved was cardiovascular with coronary artery disease (16), pericarditis (6) and congestive heart failure (5) being common problems. 1patient had dissect ing abdominal aortic aneurysm.
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placement therapy. 10 of these 47 patients subsequently opted to transfer to CAPD, whereas 30 patients under went 32 renal transplantations (28 cadaver donors and 4 live related donors). 13 (22%) patients were started on CAPD as the initial mode of renal replacement therapy; 7 of these have since tranferred to hemodialysis. Permanent vascular access was created in 56 patients; these include 2 CAPD patients who never transferred to hemodialysis but did have vascular access. 26 (46%) re quired hospitalization due to vascular-access-related complications, i.e. thrombosis, infections a n d /o r steal syndrome. There were no mechanical/technical prob lems or abdominal symptoms related to the presence of large native kidneys. Sytemic illnesses caused significant morbidity during ESRD life in these patients requiring hospitalization in some but not all instances. The details of the systemic illnesses diagnosed after initiation of ESRD therapy and their frequency are shown in table 1. Infections were by far the leading cause of morbidity in these patients and a vast majority were related to ADPKD or renal replacement therapy. There were 20 episodes of infections related to vascular access and. among 23 patients who were on CAPD at some time or other, 7 patient (30%) developed 15 episodes of peritoni tis. 4 of them had frequent relapsing peritonitis necessi tating removal of Teckhoff catheter. Peritonitis was sec ondary to presumed intestinal perforation in 1 patient on CAPD (colonic diverticulosis) and 2 patients on hemodi alysis (colonic diverticulosis and ischemic necrosis of the small bowel in 1 each). 20 episodes of symptomatic uri nary tract infections were encountered in 14 patients. Bacterial pneumonia was seen in 7 patients. Orchitis, cholecystitis and meningitis occurred once each.
Singh/Hariharan
42
Table 4. Relative death risk in the ESRD population by etiology of renal disease1 Etiology of renal disease
Relative death risk
X*’
P
Chronic glomerulonephritis Diabetic nephropathy ADPKD Hypertensive nephrosclerosis B/L small kidneys Lupus nephritis
1.0
_
_.
2.10 1.15 1.16 1.54 1.83
16.73 0.21 0.60 2.37 1.86
0.0001
0.64 0.44 0.12 0.17
The etiology of ESRD had no bearing on survival in our ESRD population except for diabetic nephropathy which was attended by a significantly higher mortality (table 4). During the follow-up period, 33 (55%) patients died. The unadjusted case fatality ratio, defined as the number of deaths in a given year divided by the total number of patients at risk in that year, for the years 1981-1987 for ADPKD was not different from that for other ESRD patients. Infections and cardiovascular dis eases were the leading causes of death in these patients (table 5).
1 Relative to a 45-year-old white female with no risk factors and a diagnosis of chronic glomerulonephritis. B /L = Bilateral.
Table 5. Cause of death in ADPKD patients on renal replace ment therapy Infections Coronary artery disease Pulmonary embolism Malignancy Cerebrovascular accident, withdrawal from dialysis and uncertain Dissecting aneurysm, respiratory failure, gastrointestinal bleeding, intestinal perforation and protein-calorie malnutrition Total
10 6 3 3 2 each
1 each 33
Pulmonary diseases, excluding the infections alluded to earlier, caused considerable morbidity in 13 patients. Pulmonary embolism occurred in 7 patients (4 after transplantation and 3 on dialysis), pleural effusion in 5 and chronic obstructive lung disease in 1. The diagnosis of pulmonary embolism was based on a highly suggestive ventilation-perfusion lung scan and/or pulmonary an giography. The reason for the high incidence of this complication is not clear. Neoplastic disease was diag nosed in 10 (renal, pulmonary and skin in 2 each and colon, uterus, uterine cervix and ill-defined disseminated malignancy in 1 each). This group of patients was hospitalized on 320 occa sions; the average duration of hospital stay was 10.2 days. This translates into 10.9 hospital days/patient/year. To tal hospital stay amounted to 3% of total time at risk. ESRD-therapy-related problems accounted for half of the inpatient time (table 2). Excluding ESRD-related surgical procedures, a total of 32 surgical interventions were undertaken in these 60 patients (table 3).
The reported prevalence of ADPKD in ESRD pa tients in USA (4.4-8.9% [4], Canada (6.84%) [5], Europe (9%) [1] and Australia (9%) [I] is much higher than in Japan (2%) [1). This is partly explained by a much higher preval ence of glomerular disease in Japan (1%) compared to the western world (30-35%) [1]. The prevalence of ADPKD in the present study was 4.6%. As reported earlier [6], 85% of all ADPKD patients in the present series were whites inspite of 39% blacks in our total ESRD population. 78% of our 60 patients were started on hemodialysis as the initial ESRD treatment modality and the remaining 22% on CAPD. This distribution is readily explained by the fact that CAPD was not available in our ESRD program until mid-1979. ADPKD accounted for 7.3% of all patients on CAPD registered with the National CAPD Registry between 1981 and 1983 [7], Contrary to the theo retical concerns, the presence of large cystic kidneys did not cause any significant abdominal discomfort or other symptoms nor did it interfere with the overall efficacy of CAPD. Thus, CAPD was effective in obtaining clinical and biochemical relief of the uremic syndrome in our ADPKD population. Nephrectomies/splenectomies were a part of the standard pretransplantation prepara tion rather than for specific symptoms. We encountered 3 incidents of peritonitis related to presumed intestinal perforation (colonic diverticulosis in 2, and ischemic necrosis of small bowel in 1) in these 60 patients. 1of these patients was on CAPD and the remain ing 2 on hemodialysis. Graham et al. [8] reported that 4 of their 9 patients with ESRD due to ADPKD managed by CAPD developed peritonitis following intestinal perfo ration. 2 of these patients had colonic perforation due to diverticulosis, I necrosis of the terminal ileum and 1acute appendicitis. 2 of these patients died. On the other hand, only 2 of 125 patients with ESRD due to other causes and
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Discussion
43
ESRD Therapy in ADPKD
study [11]; however, only 2 patients in the present series had symptomatic renal neoplasm. Hida et al. [10] de scribed an interesting autopsy study dealing with 98 ADPKD patients who were treated with hemo- orperitoneal dialysis. In those patients where the exact cause of death could be defined (42% of the total), infections were the most frequent cause of death (39.8%) followed by bleeding (38.8%). Bronchopneumonia was the most fre quent infection accounting for 31% of all infections fol lowed by peritonitis which accounted for 19%. Fatal bleeding occurred most frequently from the gastrointesti nal tract (45%) followed by intracerebral and subarach noid hemorrhage (37%). Comparative data on the frequency, duration and reason for hospitalization in ADPKD patients on ESRD therapy are not available. In the present series, the total hospital stay amounted to 3% of the total time at risk and was not different from that in the non-ADPKD patients on ESRD therapy as reported earlier[12]. The total time in the hospital was evenly split between the problems re lated directly to ADPKD and ESRD therapy and to those unrelated to ADPKD and ESRD therapy. Survival analysis in ADPKD on ESRD therapy is ham pered by small numbers. Chester et al. [6], using life table analysis, reported 85% 5-year survival in ADPKD patients on hemodialysis as compared to 52% for the controls. However, the number of diabetics in their controls is not known. In the present series, the survival for ESRD pa tients with ADPKD was similar to that for the general ESRD population, excluding diabetics. Case fatality ra tios for each year from 1981 to 1987 also showed no differ ence between the mortality in ADPKD and nondiabetic ESRD patients in ourpopulation. However, mortality was significantly higherin the diabetic ESRD patients. Infections (30%) and cardiovascular diseases (18%) were the leading cause of death in the present series as ascertained on clinical grounds. However, this can be hazardous especially in light of the fact that the exact cause of death could not bedefined in 58% of 98 ADPKD patients on ESRD therapy who were autopsied [10], In the autopsy series, intracerebral and subarachnoid hemor rhage (14%), peritonitis (7%) and bronchopneumonia (4%) were the most frequent causes of death. References I Wing AJ, Brunner FP, Brynger Hoa, et al: Comparative review between dialysis and transplantation; in Drukker W, Parsons FM, Maher JF (eds): Replacement of Renal Function by Dialy sis. Boston, Nijhoff, 1983, pp 850-871.
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managed by CAPD developed acute intestinal perfora tion. Unlike their experience, peritonitis in the present series was neither more frequent nor more troublesome in ADPKD patients on CAPD compared with those on CAPD for ESRD due to other causes. While 4 patients did require catheter replacement secondary to relapsing peritonitis, no patients were withdrawn from CAPD be cause of recurrent or complicated peritonitis. Our experi ence is similar to that reported in the US National CAPD Registry [7] where no difference was found in median number of months to first, second or third episodes of peritonitis from the time CAPD was started in ADPKD patients as compared to the patients with ESRD due to other causes. Complications related to ADPKD have featured prominently during dialysis life of ADPKD patients. Lazarus et al. [9] recorded 8 patients with ADPKD who had recurrent hematuria while on dialysis; all of them required periodic blood transfusions and nephrectomy was necessary in 4. 3 patients had severe urinary tract infections with septicemia, 2 of whom required nephrec tomy. Pyelonephritis and/or pyonephrosis was dis covered at autopsy in 4 of the 98 ADPKD patients who were treated with hemodialysis or peritoneal dialysis [10]. While symptomatic urinary tract infections were diag nosed on 20 occasions in 14 patients in the present series, only a single nephrectomy was performed for pyoneph rosis in a patient on hemodialysis. There were no in stances of gross hematuria requiring blood transfusions or nephrectomy in this group of 60 patients. Chester et al. [6] also reported very few complications related to the cystic kidneys in 25 ADPKD patients on hemodialysis. To the best of our knowledge, a comprehensive assess ment of systemic diseases in ADPKD patient diagnosed after initiation of renal replacement therapy, as described in the present study, has not been reported in the litera ture. Of the problems described in the present study, infections were the only category where these complica tions were related directly to ADPKD or ESRD therapy. These included symptomatic urinary tract infections, peritonitis and infections related to vascular access. Other infectious complications, i.e. bacterial pneumo nias, orchitis, cholecystitis and meningitis, had no direct relation to ADPKD or ESRD therapy. Other systemic diseases like gastrointestinal, pulmonary and neoplastic may be more common in the dialysis population than in the population at large, but have no direct relationship either to the underlying renal disease or ESRD therapy per se. Histological evidence of renal neoplasm has been reported in a high proportion (24.1%) of patients in one
Singh/Hariharan
44
10 Hida M, Saitoh H, Satoh T : Autopsy findings in dialysis patients with polycystic disease of the kidney. Tokai J Exp Clin Med 1984;9:389-394. 11 Grégoire JR, Torres VE, Holley KE, et al: Renal epithelial hyperplastic and neoplastic proliferation in autosomal domi nant polycystic kidney disease. Am J Kidney Dis 1987:9:27-38. 12 Ito Y, Singh S, Poliak VE: Efficacy of dialysis treatment: in Grantham JJ, Gardner KD (eds): Proceedings of the First Inter national Workshop on Polycystic Kidney Disease. Kansas City, PKR Foundation, 1985, pp 160-168.
Accepted: March 16,1990 Satwant Singh, MD VA Medical Center Nephrology Section lll/H 3200 Vine Street Cincinnati, OH 45220 (USA)
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2 Garcia-Garcia G, Deddens JA, D'Achiardi-Rey R, et al: Results of treatment in patients with end-stage renal disease : A multivar iate analysis of risk factors and survival in 341 successive pa tients. Am J Kidney Dis 1985:5:10 18. 3 Cox DR: Regression models and life tables. J R Statistic Soc [Ser B] 1972;34:187-220. 4 Welling LW, Grantham JJ: Cystic and developmental diseases of the kidney: in Brenner BM, Rector FC (eds): The Kidney. Philadelphia, Saunders, 1986, vol 2, pp 1341-1376. 5 Canadian Renal Failure Register: Kidney Foundation of Ca nada. 1985, p 73. 6 Chester AC, Argy WP Jr, Rakowski TA. et al: Polycystic kidney Disease and chronic hemodialysis. Clin Nephrol 1978:10: 129-133. 7 Nolph KD, Cutler SJ, Steinberg SM, et al: Continuous ambula tory peritoneal dialysis in the United States: A three year study. Kidney Int 1985:28:198-205. 8 Graham AN, NealeTJ. Hatfield PJ.etal: F.nd-stage renal failure due to polycystic kidney diasease managed by continuous am bulatory peritoneal dialysis. NZ Med J 1986:99:491-493. 9 Lazarus JM. Bailey GL, Hampers CL. et al: Hemodialysis and transplantation in adults with polycystic renal disease. JAMA 1971:217:1821-1824.
Nephron 1991;57:40-44
Renal Replacement Therapy in Autosomal Dominant Polycystic Kidney Disease Satwant Singh. Sundaram Hariharan University of Cincinnati Medical Center, Dialysis Clinic Inc. and Veterans Administration Medical Center, Cincinnati, Ohio, USA
Keywords. Autosomal dominant polycystic kidney disease • Renal replacement therapy • Morbidity • Mortality • Hemodialysis • Peritoneal dialysis • Renal transplantation Abstract. Autosomal dominant polycystic kidney disease (ADPKD) accounted for 4.6% of our end-stage renal disease (ESRD) population. Initial ESRD therapy consisted of hemodialysis in 78% and continuous ambulatory peritoneal dialysis in 22% with significant intertherapy transfers. Half of these patients underwent one or more renal transplantations. Infections, primarily related to ADPKD or ESRD therapy, were the leading cause of morbidity in these patients. 3% of total time on ESRD therapy was spent in hospital, half of it due to problems related to ADPKD and ESRD therapy. Overall mortality and morbidity (as measured by hospitalization rates) in ADPK D patients were similar to those in a non diabetic ESRD population.
Autosomal dominant polycystic kidney disease (ADPKD) is an important cause of end-stage renal dis ease (ESRD) accounting for 2-9% of this population worldwide [1]. The paucity of information about the clini cal characteristics of ADPKD patients with ESRD prompted us to analyze our data in 60 such patients. The objective of this study was to assess morbidity and mor tality in this population and compare these to those in a nondiabetic ESRD population.
Patients and Methods The diagnosis of ADPKD was made at or before the onset of ESRD therapy by history, physical examination and radiological studies such as intravenous pyelography, ultrasonography and/or computed tomographic scan. The study cases were drawn from patients who received some form of renal replacement therapy at the University of Cincinnati Medical Center (UCMC), Dialysis Clinic Inc. (DCI) or Veterans Administration Medical Center (VAMC), Cincinnati, betweeen January 1973 and December 1987. A compu terized data base developed at the UCMC Division of Nephrology [2] has been used for day-to-day management and record keeping of ESRD patients. The clinical characteristics of these patients were analyzed retrospectively from the computer data bank, aided by
chart review where indicated. The Cox proportional hazard model [3] was used to assess the influence of various factors, including ADPKD, on survival in those ESRD patients who were started on renal replacement therapy at UCMC. The morbidity and mortality in the ADPKD population were compared with those in nondia betic ESRD patients.
Results Among a total of 1,172 patients there were 54 patients (4.6%), 32 males and 22 females, with ADPKD who received renal replacement therapy between 1973 and 1987 at UCMC and DCI. In addition, there were 6 ESRD patients with ADPKD at VAMC. Thus, a total of 60 ESRD patients with ADPKD were available for analysis. The mean age at the start of ESRD treatment in these patients was 47.3 ± 15.2 years (SD). There were 51 whites, 8 blacks and I Asian followed for 1-204 months (mean 59.7 months). The average time between the diagnosis of ADPKD and the start of ESRD treatment was 8.85 ± 3.2 years. Renal replacement therapy consisted of hemodialysis, continuous ambulatory peritoneal dialysis (CAPD) and renal transplantation. A total of 47 (78%) patients were started on hemodialysis as the initial mode of renal re-
Downloaded by: King's College London 137.73.144.138 - 3/7/2018 10:51:35 PM
Introduction
41
ESRDTherapy in ADPKD
Tabic 1. Systemic diseases in ADPKD patients diagnosed after initiation of renal replacement therapy Category
Patients n
Infections Related to ADPKD/ESRD therapy Not related to ADPKD/ESRD therapy Gastrointestinal diseases Cardiovascular diseases Pulmonary diseases Neoplastic diseases Others Total
68 55 13 42 28 13 10 11 172
% 40
24 16 8 6 6 100
Table 2. Hospitalization data in ADPKD patients on ESRD therapy 107,460 Total days at risk 320 Total number of hospitalizations Average stay per hospitalization, days 10.2 10.9 Inpatient days/patient/year 3,264 Total inpatient days Total inpatient days as percent of total days at risk 3 1,642 (50%) Inpatient days related to ESRD therapy 1,152 (35%) Related to dialysis Related to transplant 491 (15%) 1,621 (50%) Inpatient days not related to ESRD therapy
Table 3. Surgical intervention in ADPKD patients while on ESRD treatment S u rg e ry re la te d to A D P K D /E S R D
Vascular access Peritoneal access lransplantation Pretransplantation nephrectomy/splenectomy Parathyroidectomy Total
68 20 32 18 4 142
S u rg e ry n o t re la te d to A D P K D /E S R D
Hernia repair, urethral dilatation Occular lens extraction, colectomy, prostatectomy, hystercctomy-oopherectomy Vagotomy-pyloroplasty, pneumonectomy Others Total
5 each
Grand total
174
3 each 2 each 6 32
34 infectious episodes occurred in 30 immunosuppressed transplant patients (18 bacterial, 14 viral and 2 fungal). 3 of these proved fatal (2 fulminant cytomegalo virus infections and 1 Gram-negative septicemia). While infectious events occurred equally amongst the trans plant and dialysis patients (34 episodes in each group), infections were responsible for more deaths in the dialy sis group as compared to the transplanted group (7 vs. 3). Gastrointestinal problems were diagnosed frequently after the onset of ESRD. Peptic ulcer disease was the most common (14 patients) followed by hiatal hernia (11) and colonic diverticular disease (8), cholelithiasis (4), pancreatitis (3) and cholecystitis (2). The next most com mon system involved was cardiovascular with coronary artery disease (16), pericarditis (6) and congestive heart failure (5) being common problems. 1patient had dissect ing abdominal aortic aneurysm.
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placement therapy. 10 of these 47 patients subsequently opted to transfer to CAPD, whereas 30 patients under went 32 renal transplantations (28 cadaver donors and 4 live related donors). 13 (22%) patients were started on CAPD as the initial mode of renal replacement therapy; 7 of these have since tranferred to hemodialysis. Permanent vascular access was created in 56 patients; these include 2 CAPD patients who never transferred to hemodialysis but did have vascular access. 26 (46%) re quired hospitalization due to vascular-access-related complications, i.e. thrombosis, infections a n d /o r steal syndrome. There were no mechanical/technical prob lems or abdominal symptoms related to the presence of large native kidneys. Sytemic illnesses caused significant morbidity during ESRD life in these patients requiring hospitalization in some but not all instances. The details of the systemic illnesses diagnosed after initiation of ESRD therapy and their frequency are shown in table 1. Infections were by far the leading cause of morbidity in these patients and a vast majority were related to ADPKD or renal replacement therapy. There were 20 episodes of infections related to vascular access and. among 23 patients who were on CAPD at some time or other, 7 patient (30%) developed 15 episodes of peritoni tis. 4 of them had frequent relapsing peritonitis necessi tating removal of Teckhoff catheter. Peritonitis was sec ondary to presumed intestinal perforation in 1 patient on CAPD (colonic diverticulosis) and 2 patients on hemodi alysis (colonic diverticulosis and ischemic necrosis of the small bowel in 1 each). 20 episodes of symptomatic uri nary tract infections were encountered in 14 patients. Bacterial pneumonia was seen in 7 patients. Orchitis, cholecystitis and meningitis occurred once each.
Singh/Hariharan
42
Table 4. Relative death risk in the ESRD population by etiology of renal disease1 Etiology of renal disease
Relative death risk
X*’
P
Chronic glomerulonephritis Diabetic nephropathy ADPKD Hypertensive nephrosclerosis B/L small kidneys Lupus nephritis
1.0
_
_.
2.10 1.15 1.16 1.54 1.83
16.73 0.21 0.60 2.37 1.86
0.0001
0.64 0.44 0.12 0.17
The etiology of ESRD had no bearing on survival in our ESRD population except for diabetic nephropathy which was attended by a significantly higher mortality (table 4). During the follow-up period, 33 (55%) patients died. The unadjusted case fatality ratio, defined as the number of deaths in a given year divided by the total number of patients at risk in that year, for the years 1981-1987 for ADPKD was not different from that for other ESRD patients. Infections and cardiovascular dis eases were the leading causes of death in these patients (table 5).
1 Relative to a 45-year-old white female with no risk factors and a diagnosis of chronic glomerulonephritis. B /L = Bilateral.
Table 5. Cause of death in ADPKD patients on renal replace ment therapy Infections Coronary artery disease Pulmonary embolism Malignancy Cerebrovascular accident, withdrawal from dialysis and uncertain Dissecting aneurysm, respiratory failure, gastrointestinal bleeding, intestinal perforation and protein-calorie malnutrition Total
10 6 3 3 2 each
1 each 33
Pulmonary diseases, excluding the infections alluded to earlier, caused considerable morbidity in 13 patients. Pulmonary embolism occurred in 7 patients (4 after transplantation and 3 on dialysis), pleural effusion in 5 and chronic obstructive lung disease in 1. The diagnosis of pulmonary embolism was based on a highly suggestive ventilation-perfusion lung scan and/or pulmonary an giography. The reason for the high incidence of this complication is not clear. Neoplastic disease was diag nosed in 10 (renal, pulmonary and skin in 2 each and colon, uterus, uterine cervix and ill-defined disseminated malignancy in 1 each). This group of patients was hospitalized on 320 occa sions; the average duration of hospital stay was 10.2 days. This translates into 10.9 hospital days/patient/year. To tal hospital stay amounted to 3% of total time at risk. ESRD-therapy-related problems accounted for half of the inpatient time (table 2). Excluding ESRD-related surgical procedures, a total of 32 surgical interventions were undertaken in these 60 patients (table 3).
The reported prevalence of ADPKD in ESRD pa tients in USA (4.4-8.9% [4], Canada (6.84%) [5], Europe (9%) [1] and Australia (9%) [I] is much higher than in Japan (2%) [1). This is partly explained by a much higher preval ence of glomerular disease in Japan (1%) compared to the western world (30-35%) [1]. The prevalence of ADPKD in the present study was 4.6%. As reported earlier [6], 85% of all ADPKD patients in the present series were whites inspite of 39% blacks in our total ESRD population. 78% of our 60 patients were started on hemodialysis as the initial ESRD treatment modality and the remaining 22% on CAPD. This distribution is readily explained by the fact that CAPD was not available in our ESRD program until mid-1979. ADPKD accounted for 7.3% of all patients on CAPD registered with the National CAPD Registry between 1981 and 1983 [7], Contrary to the theo retical concerns, the presence of large cystic kidneys did not cause any significant abdominal discomfort or other symptoms nor did it interfere with the overall efficacy of CAPD. Thus, CAPD was effective in obtaining clinical and biochemical relief of the uremic syndrome in our ADPKD population. Nephrectomies/splenectomies were a part of the standard pretransplantation prepara tion rather than for specific symptoms. We encountered 3 incidents of peritonitis related to presumed intestinal perforation (colonic diverticulosis in 2, and ischemic necrosis of small bowel in 1) in these 60 patients. 1of these patients was on CAPD and the remain ing 2 on hemodialysis. Graham et al. [8] reported that 4 of their 9 patients with ESRD due to ADPKD managed by CAPD developed peritonitis following intestinal perfo ration. 2 of these patients had colonic perforation due to diverticulosis, I necrosis of the terminal ileum and 1acute appendicitis. 2 of these patients died. On the other hand, only 2 of 125 patients with ESRD due to other causes and
Downloaded by: King's College London 137.73.144.138 - 3/7/2018 10:51:35 PM
Discussion
43
ESRD Therapy in ADPKD
study [11]; however, only 2 patients in the present series had symptomatic renal neoplasm. Hida et al. [10] de scribed an interesting autopsy study dealing with 98 ADPKD patients who were treated with hemo- orperitoneal dialysis. In those patients where the exact cause of death could be defined (42% of the total), infections were the most frequent cause of death (39.8%) followed by bleeding (38.8%). Bronchopneumonia was the most fre quent infection accounting for 31% of all infections fol lowed by peritonitis which accounted for 19%. Fatal bleeding occurred most frequently from the gastrointesti nal tract (45%) followed by intracerebral and subarach noid hemorrhage (37%). Comparative data on the frequency, duration and reason for hospitalization in ADPKD patients on ESRD therapy are not available. In the present series, the total hospital stay amounted to 3% of the total time at risk and was not different from that in the non-ADPKD patients on ESRD therapy as reported earlier[12]. The total time in the hospital was evenly split between the problems re lated directly to ADPKD and ESRD therapy and to those unrelated to ADPKD and ESRD therapy. Survival analysis in ADPKD on ESRD therapy is ham pered by small numbers. Chester et al. [6], using life table analysis, reported 85% 5-year survival in ADPKD patients on hemodialysis as compared to 52% for the controls. However, the number of diabetics in their controls is not known. In the present series, the survival for ESRD pa tients with ADPKD was similar to that for the general ESRD population, excluding diabetics. Case fatality ra tios for each year from 1981 to 1987 also showed no differ ence between the mortality in ADPKD and nondiabetic ESRD patients in ourpopulation. However, mortality was significantly higherin the diabetic ESRD patients. Infections (30%) and cardiovascular diseases (18%) were the leading cause of death in the present series as ascertained on clinical grounds. However, this can be hazardous especially in light of the fact that the exact cause of death could not bedefined in 58% of 98 ADPKD patients on ESRD therapy who were autopsied [10], In the autopsy series, intracerebral and subarachnoid hemor rhage (14%), peritonitis (7%) and bronchopneumonia (4%) were the most frequent causes of death. References I Wing AJ, Brunner FP, Brynger Hoa, et al: Comparative review between dialysis and transplantation; in Drukker W, Parsons FM, Maher JF (eds): Replacement of Renal Function by Dialy sis. Boston, Nijhoff, 1983, pp 850-871.
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managed by CAPD developed acute intestinal perfora tion. Unlike their experience, peritonitis in the present series was neither more frequent nor more troublesome in ADPKD patients on CAPD compared with those on CAPD for ESRD due to other causes. While 4 patients did require catheter replacement secondary to relapsing peritonitis, no patients were withdrawn from CAPD be cause of recurrent or complicated peritonitis. Our experi ence is similar to that reported in the US National CAPD Registry [7] where no difference was found in median number of months to first, second or third episodes of peritonitis from the time CAPD was started in ADPKD patients as compared to the patients with ESRD due to other causes. Complications related to ADPKD have featured prominently during dialysis life of ADPKD patients. Lazarus et al. [9] recorded 8 patients with ADPKD who had recurrent hematuria while on dialysis; all of them required periodic blood transfusions and nephrectomy was necessary in 4. 3 patients had severe urinary tract infections with septicemia, 2 of whom required nephrec tomy. Pyelonephritis and/or pyonephrosis was dis covered at autopsy in 4 of the 98 ADPKD patients who were treated with hemodialysis or peritoneal dialysis [10]. While symptomatic urinary tract infections were diag nosed on 20 occasions in 14 patients in the present series, only a single nephrectomy was performed for pyoneph rosis in a patient on hemodialysis. There were no in stances of gross hematuria requiring blood transfusions or nephrectomy in this group of 60 patients. Chester et al. [6] also reported very few complications related to the cystic kidneys in 25 ADPKD patients on hemodialysis. To the best of our knowledge, a comprehensive assess ment of systemic diseases in ADPKD patient diagnosed after initiation of renal replacement therapy, as described in the present study, has not been reported in the litera ture. Of the problems described in the present study, infections were the only category where these complica tions were related directly to ADPKD or ESRD therapy. These included symptomatic urinary tract infections, peritonitis and infections related to vascular access. Other infectious complications, i.e. bacterial pneumo nias, orchitis, cholecystitis and meningitis, had no direct relation to ADPKD or ESRD therapy. Other systemic diseases like gastrointestinal, pulmonary and neoplastic may be more common in the dialysis population than in the population at large, but have no direct relationship either to the underlying renal disease or ESRD therapy per se. Histological evidence of renal neoplasm has been reported in a high proportion (24.1%) of patients in one
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10 Hida M, Saitoh H, Satoh T : Autopsy findings in dialysis patients with polycystic disease of the kidney. Tokai J Exp Clin Med 1984;9:389-394. 11 Grégoire JR, Torres VE, Holley KE, et al: Renal epithelial hyperplastic and neoplastic proliferation in autosomal domi nant polycystic kidney disease. Am J Kidney Dis 1987:9:27-38. 12 Ito Y, Singh S, Poliak VE: Efficacy of dialysis treatment: in Grantham JJ, Gardner KD (eds): Proceedings of the First Inter national Workshop on Polycystic Kidney Disease. Kansas City, PKR Foundation, 1985, pp 160-168.
Accepted: March 16,1990 Satwant Singh, MD VA Medical Center Nephrology Section lll/H 3200 Vine Street Cincinnati, OH 45220 (USA)
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2 Garcia-Garcia G, Deddens JA, D'Achiardi-Rey R, et al: Results of treatment in patients with end-stage renal disease : A multivar iate analysis of risk factors and survival in 341 successive pa tients. Am J Kidney Dis 1985:5:10 18. 3 Cox DR: Regression models and life tables. J R Statistic Soc [Ser B] 1972;34:187-220. 4 Welling LW, Grantham JJ: Cystic and developmental diseases of the kidney: in Brenner BM, Rector FC (eds): The Kidney. Philadelphia, Saunders, 1986, vol 2, pp 1341-1376. 5 Canadian Renal Failure Register: Kidney Foundation of Ca nada. 1985, p 73. 6 Chester AC, Argy WP Jr, Rakowski TA. et al: Polycystic kidney Disease and chronic hemodialysis. Clin Nephrol 1978:10: 129-133. 7 Nolph KD, Cutler SJ, Steinberg SM, et al: Continuous ambula tory peritoneal dialysis in the United States: A three year study. Kidney Int 1985:28:198-205. 8 Graham AN, NealeTJ. Hatfield PJ.etal: F.nd-stage renal failure due to polycystic kidney diasease managed by continuous am bulatory peritoneal dialysis. NZ Med J 1986:99:491-493. 9 Lazarus JM. Bailey GL, Hampers CL. et al: Hemodialysis and transplantation in adults with polycystic renal disease. JAMA 1971:217:1821-1824.
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