Letter to the Editor Am J Nephrol 1992;12:279-280

a Servicio de Nefrología y b Servicio de Anatomía Patológica, Hospital General ‘Gregorio Marañón’. Madrid, España

Membranous Glomerulonephritis after Kidney Transplantation and Urologie Complications

Dear Sir, Membranous glomerulonephritis (MGN) is an uncom­ mon complication of renal transplantation. Recurrent MGN is rare, as of 1988 less than 20 cases had been reported [1], In contrast, de novo MGN occurs more fre­ quently [2], approximately 100 cases of de novo MGN have been reported [3, 4], although the causes of de novo MGN after kidney transplantation have not been eluci­ dated. We report the clinicopathologic features of 8 cases of MGN detected at our institute and the unusual inci­ dence of urological complications in our patients. During a 13-year period ( 1976-1988), 427 renal trans­ plants were performed at Hospital General ‘Gregorio Maranon’ (353 adults, 74 children). Twenty-nine (6.8%) patients presented proteinuria greater than 1.5 g/24 h and then a percutaneous renal biopsy was performed. From them, renal biopsies documented 1 case of recurrent MGN (incidence: 0.23% of all grafts, 3.4% of performed biopsies) and 6 of de novo MGN (1.4% of all grafts, 20.7% of biopsied cases). Another positive biopsy was performed in a patient who had been transplanted at another hospital and then transferred to us. Tissue speci­ mens were processed for light microscopy and immuno­ fluorescence according to standard techniques. The 8 patients with MGN ranged in age from 15 to 53 years (mean 33.2 ± 5.3, values expressed as mean ± SEM). One patient had serological evidence of hepatitis B. but immunofluorescence with antihepatitis B antise­ rum was negative. None of the other patients had clinical or serological evidence of systemic disease or had re­

Received: August 17,1990 Accepted: May II. 1992

ceived drugs known to be associated with MGN. Two patients received antithymocyte globulin as treatment, but the development of MGN was not temporally related to this therapy in 1 of these patients. The degree of HLA class 1 and class II antigens match­ ing followed no set pattern. The presence of MGN was first documented at biopsy 2-36 months after transplan­ tation (mean 14.3 ± 4.0). Five patients presented with nephrotic syndrome, the remaining 3 patients experi­ enced only proteinuria (1.5-12 g/day, mean 6.8 ± 1.4) with or without hematuria. All of the patients have main­ tained functioning grafts for 8-84 months after transplan­ tation (mean 36.6 ± 10.3). Current serum creatinine ranges from 1.2 to 3 mg'dl (mean 1.9 ± 0.2). Only I patient showed impairment of the renal function, in which were associated changes of humoral chronic rejec­ tion; no other patient had chronic rejection lesions in the bioptic examination. Six patients had presented urologic complications after kidney transplantation (table 1). No therapy for MGN was instituted. The pathogenesis of MGN is poorly understood. MGN was thought to be caused by preformed circulating im­ mune complexes; more recently, experimental studies have provided evidence that MGN could be the result of an in situ formation of immune complexes [5], In the best studied animal model of MGN, Heymann’s nephritis or autologous immune complex nephropathy, subepithelial immune deposits are apparently formed by antibody to an antigen present in the brush border of proximal tubu-

Dr. N.R. Robles Pérez Sección de Nefrología Hospital Regional ’Infanta Cristina' Ctra dc Portugal s/n H-06006 Badajoz (Spain)

© 1992 S. Karger AG. Basel 0250-8095/92/0124-0279 S2.75/0

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Nicolás R. Roblesa Francisco Gomez-Campderaa Fernando Anayaa Enrique Niembrob Fernando Valderrabanoa

Table 1 Patient No.

Age

Sex

Etiology

1

15

F

2 3 4 5 6 7

37 41 16 53 34 20

F F F M F F

8

50

F

malformative uropathy MGN amyloidosis FSG CPN VUR + FSG familial nephrop­ athy polyschistosis

Urological complication

urinary leak urinary leak urethrovesicai stenosis urinary leak urethrovesicai stenosis short urether

FSG = Focal segmental glomerulosclerosis: CPN = chronic pyelo­ nephritis; VUR = vesicoureteral reflux.

lar epithelial cells [6]. Data to support a role for tubular brush border antigens in human MGN has been reported by several authors [7, 8]. The possibility that ureteric obstruction could have played a pathogenetic role in the glomerular lesion in our patient should also be considered. The association be­

tween vesicoureteric reflux and glomerulonephritis has been reported in both and transplanted kidney [9, 10], The glomerular lesion in most cases is one of focal and segmental hyalinosis or membranoproliferative glomeru­ lonephritis but the association between MGN and vesi­ coureteric reflux has also been noted. It has been sug­ gested that ureteric problems may, through increased back pressure, release immunogenic tubular antigens with consequent antibody and complex formation [ 10]. Re­ cently, presence of circulating antibodies against brush border antigens in a patient with membranous nephropa­ thy and bilateral pyeloureteral stenosis has been reported [ 11 ]. In this way, the association between ureteric obstruc­ tion posttransplant and de novo MGN has been pre­ viously reported [12], 75% of our patients with MGN suf­ fered urological complications; this is very striking, espe­ cially if it takes into account that the global incidence of urological complications at our institute from 1976 to 1987 was 15.3% (10.3% urinary leaks, 4.2% ureteric obstruction) [13]. Furthermore, a significant binding of IgG to the tubule was noted in one bioptic specimen. MGN seems to be a rare complication of kidney trans­ plantation with benign prognosis when chronic rejection is not associated. Patients with urological complications could have a higher risk of developing this complication.

R eferences

280

6 Douglas MF, Rabideau DP. Schwartz MM, Le­ wis EJ: Evidence of autologous immune-com­ plex nephritis. N Engl J Med 1981:305:13261329. 7 Zanetti M. Mandet C, Duboust A. Bedrossian J. Bariety J: Demonstration of passive Heymann's nephritis-like mechanism in a human kidney transplant. Clin Nephrol 1981:155: 272-277. 8 Naruse T, Kitamura K, Miyakawa Y, Shibata S: Deposition of renal tubular epithelial anti­ gen along the glomerular capillary walls of pa­ tients with membranous glomerulonephritis. J Immunol 1973;110:1163-1166. 9 Kincaid-Smith P: Glomerular and vascular le­ sions in atrophic chronic pyelonephritis and reflux nephropathy. Adv Nephrol 1975;5:3—

11 Gonzalez-Cabrero J. de Nicolas R. Ortiz A. Mampaso F. Hernando L, Egido J: Presence of circulating antibodies against brush border an­ tigens (F X 1A) in a patient with membranous nephropathy and bilateral pyeloureteral steno­ sis. Comparison with idiopathic membranous nephropathy. Nephrol Dial Trasplant 1992:7: 293-299. 12 Lieberthal W. Bernard DB. Donohoe JF. Stilmant MM, Couser WG: Rapid recurrence of membranous nephropathy in a related kidney allograft. Clin Nephrol 1979:12:222-228. 13 Franco Esteve A, Anaya Fernandez-Lomana F, Fernandez de Caleya D, et al: Complicaciones urológicas en 280 trasplantes renales. Acta UrolEsp 1988;12:217-222.

17.

10 Mathew TH. Kincaid-Smith P, Vikraman P: Risks of vesicoureteric reflux in the trans­ planted kidney. N Engl J Med 1977:297:414— 418.

Robles/Gomez-Campdera/Anaya/Niembro/ Valderrabano

Membranous Nephropathy after Kidney Transplantation

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1 Antignac C. Hinglais N. Gubler MC, Gagnadoux MF. Broyer M. Habib R: De novo mem­ branous glomerulonephritis in renal allografts in children. Clin Nephrol 1988:30:1-7. 2 Ward HJ. Rafjer J. Farrer JH. Glassock RJ. Dumke A: Recurrent disease, pregnancy and long-term issues; in Gavoroy MR, Guttman RD (eds): Renal Transplantation. New York, Churchill Livingstone, 1986, pp 273-339. 3 Berger BE, Vicentini F, Biava C, Amend WJ, Feduska N, Salvatierra O: De novo and recur­ rent membranous glomerulopathy following kidney transplantation. Transplantation 1983: 35:315-319. 4 Truong L, Gelfand J, D’Agati V, Tomaszewski J, Appel G, Hardy M, Pirani L: De novo mem­ branous glomerulonephropathy in renal allo­ grafts: A report of ten cases and review of the literature. Am J Kidney Dis 1989; 14:131- 144. 5 Couser WG: Mechanisms of glomerular injury in inmune-complex disease. Kidney Int 1985; 28:569-583.

Membranous glomerulonephritis after kidney transplantation and urologic complications.

Letter to the Editor Am J Nephrol 1992;12:279-280 a Servicio de Nefrología y b Servicio de Anatomía Patológica, Hospital General ‘Gregorio Marañón’...
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