British Journal of Urology (1991), 67,241-245 01991 British Journal of Urology
Acute Changes in Kidney Function following Extracorporeal Shock Wave Lithotripsy for Renal Stones S. J. KARLSEN and K. J. BERG Section of Urology, Department of Surgery, Aker Hospital and Section of Nephrology, Medical Department B. The National Hospital, Oslo, Norway
Summary-Seventeen patients were subjected to analysis of various renal functional parameters before and after extracorporeal shoclk wave lithotripsy (ESWL) for renal stones. Thirteen patients were observed a t 2 weeks and 3 months. Glomerular filtration rate (GFR) was not influenced by ESWL as based on unchanged serum levels of creatinine, microglo globulin and creatinine clearance. A significant increase in urinary excretion of microglo globulin, N-acetyl-Bglucosaminidase and alkaline phosphatase, with return to pre-treatment values within 4 to 5 days, reflected transient disturbances in proximal tubular function. Urinary albumin excretion was increased 0-24 h after ESWL. No siginificant alterations were observed in plasma renin activity or serum aldosterone due to ESWL. Serum lactic dehydrogenase remained significantly increased for 2 weeks. In addition, significant changes in several blood and urine parameterswere caused by immersion in water and intravenous iinfusions during treatment and were not specifically due to ESWL.
Since the introduction of ESWL to clinical practice (Chaussy et al., 1982), the results of llarge clinical series have shown that extracorporeall shock wave lithotripsy is effective in stone disintegration. Side effects, however, do occur. Magnetic resonance imaging (MRI) has detected renal injury in up to 85% of patients (Baumgartner et al., 1987) and several authors have reported morphological and functional changes based on lboth animal experiments and clinical investigations (Lingeman et al., 1988). The significance of any physiological change following ESWL is unknown. A causal.relationship to the development of hypertension has been postulated in a small percentage of patients (Williams etal., 1987). In our controlled studies on acute renal changes following extracorporeal shock wave exposure to 1 kidney in dogs (Karlsen et al., 1990a and b), changes were detected in glomei-ular,tubular and renal vascular morphology and function. In the exposed kidney, effective renal plasma flow (ERPF) Accepted for publication 7 August 1990
decreased significantly, while glomerular filtration rate was unchanged. Filtration fraction increased in both kidneys. A non-significant rise in plasma renin activity (PRA), most marked in the renal vein blood from the exposed kidney, was noted. A significant rise in urinary excretion of N-acetyl-Pglucosaminidase (U-NAG) and fall in the extraction of para-amino-hippuric acid (PAH) in the exposed kidney reflected damage to proximal tubular function. Despite the extensive use of ESWL, knowledge of possible clinical side effects is limited. Detailed studies are therefore required and a prospective clinical study was designed to investigate acute changes in renal function following ESWL of renal stones. Patients and Methods
Seventeen patients, 10 women and 7 men (mean age 51.8 years; range 18-72) with stones in the renal pelvis and/or calices were studied. All had a total stone burden less than 2.5 cm in diameter. Patients
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2225 & 787 pg/l and the urinary excretion was 137f 66 pg/24 h. The within assay coefficient of variation was 5% in serum and 7.7% in urine. Urine volume (UV) was measured in ml/min. Urinary albumin excretion (pg/24 h) was determined by an RIA kit (Pharmacia AB, Uppsala, Sweden). The excretion in healthy controls was4.0 f2.6 yg/24 h. The within assay coefficient of variation was 9%. Urine and serum osmolalities (m Osmol/kg) were determined by the freezing point depression method (Hermann Roebling Osmometer, Berlin, W. Germany). Urinary alkaline phosphatase (ALP) (units/mmol creatinine) was measured by photospectrometry using a commercial kit (Boehringer, Mannheim GmbH Diagnostica, W. Germany). The mean value in the reference material was 0.188 f0.077 units/mmol creatinine. The within assay coefficient of variation was 3.7%. Urinary NAG (units/ymol creatinine) was determined by the fluorometric method of Price et al. (1970) using methylumbelliferylglucosaminidine as substrate. The mean value in the reference material was 5.4 f2.3 units/pmol creatinine. The within assay coefficient of variation was 3%. PRA (nmol/l/h) was determined by radiommunoassay of angiotensin I before and after incubation of plasma samples according to Sundsfjord (1971). The normal range for ambulatory patients is 0.5-1.5 nmol/l/h; the within assay coefficient of variation for the method was 8%. Serum aldosterone (picomol/l) was measured by radioimmunoassay, using reagents from Diagnostic Analytical methods. Creatinine (pmolil) in serum Product Cooperation (DPC). This radioimmunoas(mean normal valuef 1SD= 88.4f 12.6) and urine say employs 2sIlabelled aldosterone and antibodywere determined by a rate-dependent modification coated tubes. The normal range for ambulatory of the Jaffe reaction using a creatinine analyser patients is 70-450 picomol/l; the within assay (Beckman model 2). All clearance values were coefficient of variation was 5%. Endogenous clearcorrected to 1.73 m2body surface. j?2-microglobulin ance of creatinine (CCr,ml/min) was used as index in serum (pg/l) and urine (pg/24 h) were assayed by for GFR. Osmolal clearance (Cosmol, ml/min) and a commercial radioimmunoassay (RIA) kit (Phar- free water clearance (CHZO, ml/min) were calculated macia AB, Uppsala, Sweden). Urine was stored at using conventional formulae. pH > 6 . The serum values in healthy controls were Haemoglobin (Hb, g/dl), haematocrit (Hct, %), white blood cell count (WBC, 109/1),red blood cell Table 1 Changes in Blood Variables in 4 Patients before count (RBC, l0l2/l), haptoglobin (g/l), serum uric and after Immersion in Water for 25 min prior to ESWL acid (pmol/l), plasma protein (g/l), albumin (g/l), serum and urinary electrolytes (mmol/l) and serum Before immersion After immersion lactic dehydrogenase (LD, U/1) were measured by Mean fSEM Variable Mean k SEM conventional methods. 0.40+0.01 Hct (%I 0.45f0.01 The mean of the measured values obtained before 301 k 0 . 9 Osmolality (m Osmol/l) 302 f0.8 and after ESWL were calculated. The mean and 62.2+ 1.4 Protein (g/l) 75.2k3.4 standard error of the mean (SEM) are used for the 37.5 1.0 Albumin (g/l) 46.0 & 0.4 140.2+0.9 N a (mmol/l) 143.5+0.3 presentation. The means of the values obtained 4.4 f0.1 K (mmolil) 3.6k0.5 before (control) and at each of the tests after ESWL PRA (nmol/l/h) 1 . 1 k0.5 0.5 k0.3 were compared statistically by the 2-tailed WilAldosterone (picomol/l) 316.5 f 31.6 153.5 k 10.7 coxon signed rank test.
with any sign of obstruction on intravenous urography (IVU) prior to treatment were excluded. Two 24-h urine collections were sampled during the 2 days preceding treatment and 2 after, at 024 h and day 4-5. Blood tests were carried out on the same 2 days before ESWL, 1 immediately after, and then daily for 2 days. Clinical follow-up with 24-h urine samples and blood tests were performed in 13patients 2 weeks and 3 months after treatment. In 4 patients additional blood samples were obtained after immersion for 25 min in the water bath, immediately prior to ESWL, to evaluate the effects of premedication, sedation, intravenous infusion and water immersion (Table 1). The patients were deprived of food and water from mid-night on the preceding day. Intravenous infusions of 1000 ml5% glucose and 1000 ml normal saline were administered for 2 h during and after treatment and unlimited oral fluids were allowed thereafter. The patients were premedicated with pethidine 1 mg/kg. During treatment small doses of intravenous analgesics and sedatives were administered according to individual needs (mean 0.08 mg phentanyl and 1.82 mg benzodiazepine). ESWL was performed by the modified Dornier HM3 lithotriptor (Graff et al., 1988). The mean number of exposures was 2253 (range 1000-3000), delivered at 18-20 kV. The mean duration of water immersion was 23 min (range 15-20), the water temperature being constant at 37°C.
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243
ACUTE CHANGES IN KIDNEY FUNCTION FOLLOWING ESWL FOR RENAL STONES
Urinary exretion of proteins (albumin and p2microglobulin) increased significantly during the first 24 h after ESWL (Table 4). Urinary enzyme excretion (NAG and ALP) was also elevated. Pretreatment values were obtained on day 4-5. S-LD increased from 352 k 15.8 U/1before ESWL to 419k15.3 U/1 after ( P < O . O O l ) and remained high 2 weeks after treatment (P
Acute Changes in Kidney Function following Extracorporeal Shock Wave Lithotripsy for Renal Stones S. J. KARLSEN and K. J. BERG Section of Urology, Department of Surgery, Aker Hospital and Section of Nephrology, Medical Department B. The National Hospital, Oslo, Norway
Summary-Seventeen patients were subjected to analysis of various renal functional parameters before and after extracorporeal shoclk wave lithotripsy (ESWL) for renal stones. Thirteen patients were observed a t 2 weeks and 3 months. Glomerular filtration rate (GFR) was not influenced by ESWL as based on unchanged serum levels of creatinine, microglo globulin and creatinine clearance. A significant increase in urinary excretion of microglo globulin, N-acetyl-Bglucosaminidase and alkaline phosphatase, with return to pre-treatment values within 4 to 5 days, reflected transient disturbances in proximal tubular function. Urinary albumin excretion was increased 0-24 h after ESWL. No siginificant alterations were observed in plasma renin activity or serum aldosterone due to ESWL. Serum lactic dehydrogenase remained significantly increased for 2 weeks. In addition, significant changes in several blood and urine parameterswere caused by immersion in water and intravenous iinfusions during treatment and were not specifically due to ESWL.
Since the introduction of ESWL to clinical practice (Chaussy et al., 1982), the results of llarge clinical series have shown that extracorporeall shock wave lithotripsy is effective in stone disintegration. Side effects, however, do occur. Magnetic resonance imaging (MRI) has detected renal injury in up to 85% of patients (Baumgartner et al., 1987) and several authors have reported morphological and functional changes based on lboth animal experiments and clinical investigations (Lingeman et al., 1988). The significance of any physiological change following ESWL is unknown. A causal.relationship to the development of hypertension has been postulated in a small percentage of patients (Williams etal., 1987). In our controlled studies on acute renal changes following extracorporeal shock wave exposure to 1 kidney in dogs (Karlsen et al., 1990a and b), changes were detected in glomei-ular,tubular and renal vascular morphology and function. In the exposed kidney, effective renal plasma flow (ERPF) Accepted for publication 7 August 1990
decreased significantly, while glomerular filtration rate was unchanged. Filtration fraction increased in both kidneys. A non-significant rise in plasma renin activity (PRA), most marked in the renal vein blood from the exposed kidney, was noted. A significant rise in urinary excretion of N-acetyl-Pglucosaminidase (U-NAG) and fall in the extraction of para-amino-hippuric acid (PAH) in the exposed kidney reflected damage to proximal tubular function. Despite the extensive use of ESWL, knowledge of possible clinical side effects is limited. Detailed studies are therefore required and a prospective clinical study was designed to investigate acute changes in renal function following ESWL of renal stones. Patients and Methods
Seventeen patients, 10 women and 7 men (mean age 51.8 years; range 18-72) with stones in the renal pelvis and/or calices were studied. All had a total stone burden less than 2.5 cm in diameter. Patients
24 1
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BRITISH JOURNAL OF UROLOGY
2225 & 787 pg/l and the urinary excretion was 137f 66 pg/24 h. The within assay coefficient of variation was 5% in serum and 7.7% in urine. Urine volume (UV) was measured in ml/min. Urinary albumin excretion (pg/24 h) was determined by an RIA kit (Pharmacia AB, Uppsala, Sweden). The excretion in healthy controls was4.0 f2.6 yg/24 h. The within assay coefficient of variation was 9%. Urine and serum osmolalities (m Osmol/kg) were determined by the freezing point depression method (Hermann Roebling Osmometer, Berlin, W. Germany). Urinary alkaline phosphatase (ALP) (units/mmol creatinine) was measured by photospectrometry using a commercial kit (Boehringer, Mannheim GmbH Diagnostica, W. Germany). The mean value in the reference material was 0.188 f0.077 units/mmol creatinine. The within assay coefficient of variation was 3.7%. Urinary NAG (units/ymol creatinine) was determined by the fluorometric method of Price et al. (1970) using methylumbelliferylglucosaminidine as substrate. The mean value in the reference material was 5.4 f2.3 units/pmol creatinine. The within assay coefficient of variation was 3%. PRA (nmol/l/h) was determined by radiommunoassay of angiotensin I before and after incubation of plasma samples according to Sundsfjord (1971). The normal range for ambulatory patients is 0.5-1.5 nmol/l/h; the within assay coefficient of variation for the method was 8%. Serum aldosterone (picomol/l) was measured by radioimmunoassay, using reagents from Diagnostic Analytical methods. Creatinine (pmolil) in serum Product Cooperation (DPC). This radioimmunoas(mean normal valuef 1SD= 88.4f 12.6) and urine say employs 2sIlabelled aldosterone and antibodywere determined by a rate-dependent modification coated tubes. The normal range for ambulatory of the Jaffe reaction using a creatinine analyser patients is 70-450 picomol/l; the within assay (Beckman model 2). All clearance values were coefficient of variation was 5%. Endogenous clearcorrected to 1.73 m2body surface. j?2-microglobulin ance of creatinine (CCr,ml/min) was used as index in serum (pg/l) and urine (pg/24 h) were assayed by for GFR. Osmolal clearance (Cosmol, ml/min) and a commercial radioimmunoassay (RIA) kit (Phar- free water clearance (CHZO, ml/min) were calculated macia AB, Uppsala, Sweden). Urine was stored at using conventional formulae. pH > 6 . The serum values in healthy controls were Haemoglobin (Hb, g/dl), haematocrit (Hct, %), white blood cell count (WBC, 109/1),red blood cell Table 1 Changes in Blood Variables in 4 Patients before count (RBC, l0l2/l), haptoglobin (g/l), serum uric and after Immersion in Water for 25 min prior to ESWL acid (pmol/l), plasma protein (g/l), albumin (g/l), serum and urinary electrolytes (mmol/l) and serum Before immersion After immersion lactic dehydrogenase (LD, U/1) were measured by Mean fSEM Variable Mean k SEM conventional methods. 0.40+0.01 Hct (%I 0.45f0.01 The mean of the measured values obtained before 301 k 0 . 9 Osmolality (m Osmol/l) 302 f0.8 and after ESWL were calculated. The mean and 62.2+ 1.4 Protein (g/l) 75.2k3.4 standard error of the mean (SEM) are used for the 37.5 1.0 Albumin (g/l) 46.0 & 0.4 140.2+0.9 N a (mmol/l) 143.5+0.3 presentation. The means of the values obtained 4.4 f0.1 K (mmolil) 3.6k0.5 before (control) and at each of the tests after ESWL PRA (nmol/l/h) 1 . 1 k0.5 0.5 k0.3 were compared statistically by the 2-tailed WilAldosterone (picomol/l) 316.5 f 31.6 153.5 k 10.7 coxon signed rank test.
with any sign of obstruction on intravenous urography (IVU) prior to treatment were excluded. Two 24-h urine collections were sampled during the 2 days preceding treatment and 2 after, at 024 h and day 4-5. Blood tests were carried out on the same 2 days before ESWL, 1 immediately after, and then daily for 2 days. Clinical follow-up with 24-h urine samples and blood tests were performed in 13patients 2 weeks and 3 months after treatment. In 4 patients additional blood samples were obtained after immersion for 25 min in the water bath, immediately prior to ESWL, to evaluate the effects of premedication, sedation, intravenous infusion and water immersion (Table 1). The patients were deprived of food and water from mid-night on the preceding day. Intravenous infusions of 1000 ml5% glucose and 1000 ml normal saline were administered for 2 h during and after treatment and unlimited oral fluids were allowed thereafter. The patients were premedicated with pethidine 1 mg/kg. During treatment small doses of intravenous analgesics and sedatives were administered according to individual needs (mean 0.08 mg phentanyl and 1.82 mg benzodiazepine). ESWL was performed by the modified Dornier HM3 lithotriptor (Graff et al., 1988). The mean number of exposures was 2253 (range 1000-3000), delivered at 18-20 kV. The mean duration of water immersion was 23 min (range 15-20), the water temperature being constant at 37°C.
*
243
ACUTE CHANGES IN KIDNEY FUNCTION FOLLOWING ESWL FOR RENAL STONES
Urinary exretion of proteins (albumin and p2microglobulin) increased significantly during the first 24 h after ESWL (Table 4). Urinary enzyme excretion (NAG and ALP) was also elevated. Pretreatment values were obtained on day 4-5. S-LD increased from 352 k 15.8 U/1before ESWL to 419k15.3 U/1 after ( P < O . O O l ) and remained high 2 weeks after treatment (P
