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Clinical Nephrology, Volume 61, No. 4/2004 (231-237)

Molecular and clinical studies of Dent’s disease in Japan: biochemical examination and renal ultrasonography do not predict carrier state 

T. Matsuyama¹, M. Awazu², T. Oikawa³, J. Inatomi⁴, T. Sekine⁴ and T. Igarashi⁴ 

¹Department of Pediatrics, Fussa Hospital, ²Department of Pediatrics,
Keio University School of Medicine, ³Department of Pediatrics,
Jikei University School of Medicine, ⁴Department of Pediatrics, Faculty of Medicine, The University of Tokyo, Tokyo, Japan 

Background: Dent’s disease is an X-linked renal tubular disorder characterized by low-molecular-weight-proteinuria, hypercalciuria, nephrolithiasis and renal failure. The disease is due to inactivation of a renal chloride channel gene, CLCN5. We have investigated 3 unrelated Japanese families for CLCN5 mutations and assessed the carrier mothers biochemically and ultrasonogaraphically to ascertain whether these clinical examinations can predict the carrier state of the disease. Material and methods: Twelve members from these families were studied biochemically and ultrasonographically. Leukocyte DNA from probands was used with CLCN5-specific primers for PCR amplification of the coding region and exon-intron boundaries, and the DNA sequences of the products determined to identify abnormalities in the gene. Results: Three novel CLCN5 mutations consisting of a single base “A” insertion between nucleotides 590 and 591, a nonsense mutation (R28X) and a missense mutation (G506R) were exhibited. Hypophosphatemia was detected in 2 patients, b₂-microglobulinuria, a₁-microglobulinuria, and hyper-retinol binding proteinuria in 6 patients, hypercalciuria in 5 patients, decreased urine osmolality in 3 patients, and nephrocalcinosis or nephrolithiasis in 4 patients. Biochemical analysis of the urine and the renal ultrasonography in each carrier mother were completely normal. Conclusions: Neither urinary low-molecular-weight-proteins, urinary calcium to creatinine ratio, nor renal ultrasonography was predictive of carrier state in the 3 families with this disease, although each carrier mother had CLCN5 mutation. Hypophosphatemia and decreased urine osmolality might be a hint to suspect the carrier state of Dent’s disease, although these findings are not found frequently.

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Clinical Nephrology, Volume 61, No. 4/2004 (238-245)

Preemptive treatment with oral ganciclovir for pediatric renal transplantation 

M. Melgosa Hijosa, C. García Meseguer, P. Peña García, A. Alonso Melgar, L. Espinosa Román, A. Peña Carrión and M. Navarro Torres 

Pediatric Nephrology Unit, Microbiology Unit “La Paz” Hospital, Madrid, Spain 

This prospective study examines 42 children in the first year after renal transplantation. They all received intravenous ganciclovir prophylaxis for cytomegalovirus in the immediate post-transplant period. Quantitative antigenemia (pp68) determinations and blood, urine and throat cultures were done on a scheduled basis to detect cytomegalovirus. Infection was detected in 22 children (52.4%) within an average 44.31 ± 27.38 days; 5/22 were symptomatic. The antigenemia was positive (+) in all the infected patients, and so were blood culture in 68.2%, urine culture in 59.1% and throat culture in 31.8%. A positive antigenemia was the earliest finding in all cases but 1. The 5 children with clinical symptoms received intravenous ganciclovir. Asymptomatic infected children received oral ganciclovir at an average dose of 47.64 ± 8.10 mg/kg/day (median 46.58 (range 33 – 58.7) mg/kg/day) for an average of 58.47 ± 27.76 days (median 58 (range 26 – 211) days). No patient developed disease or ganciclovir resistance during the treatment. No patient presented acute graft rejection or renal dysfunction and their glomerular filtrate rate at 1 year was similar to that of noninfected children (90.38 ± 26.51 vs. 93.93 ± 36.24 ml/min/1.73 m²). We conclude that preemptive treatment with oral ganciclovir is useful and safe in children with renal transplantation and that monitoring blood antigenemia is a sensitive and early method to detect and control CMV infection. 

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Clinical Nephrology, Volume 61, No. 4/2004 (246-252)

Cardiovascular morbidity and mortality in patients with diabetes mellitus type I after kidney transplantation: a case-control study 

V. Lufft², B. Dannenberg¹, H.J. Schlitt³, R. Pichlmayr³ and R. Brunkhorst⁴ 

¹Abteilung Nephrologie, Zentrum Innere Medizin und Dermatologie, ²Nephrologisches Zentrum Rendsburg-Eckernförde, Rendsburg,
³Klinik für Abdominal- und Transplantationschirurgie, Medizinische Hochschule Hannover, und ⁴Klinik für Nieren-, Hochdruck- und Gefäßkrankheiten, Klinikum Hannover Oststadt, Hannover, Germany 

 Background: The proportion of diabetics among patients requiring renal replacement therapy continues to increase in most western countries. The acceptance rate for renal transplantation varies among transplant centers and is influenced by the current opinion on the outcome of transplantation in diabetics. Controlled data on patient and graft survival in type I diabetics, however, are scarce. Methods: We performed a retrospective case-control analysis on patient and graft survival and the cardiovascular morbidity of patients with type I diabetes after renal transplantation versus carefully matched nondiabetic transplant recipients. Match criteria were duration of previous hemodialysis, age and date of renal transplantation. Moreover, risk factors for cardiovascular disease in uremic patients were evaluated at the time of registration for renal transplantation and at the end of the observation period. Results: Seventy-seven matched pairs were enclosed. Patient survival was significantly worse in the diabetic patients, graft survival was comparable in both groups, when graft loss because of patient’s death was censored. In the diabetic patients, risk of death (odds ratio: 4.38) as well as the prevalence of cardiovascular morbidity (odds ratio: 4.47) were significantly higher than in the matched nondiabetic controls. Cox regression analysis showed that diabetes mellitus was an independent risk factor for patient survival; no association was found with hypertension, hyperlipidemia, hyperparathyroidism, calcium × phosphate product, body mass index and HbA1c. Cardiovascular morbidity, however, was already significantly higher in the diabetic group at the time of registration. Conclusions: Diabetes mellitus type I has a dominant impact on morbidity and mortality after renal transplantation and is associated with an approximately 4-fold higher risk of death. Cardiovascular disease accounts for the significantly worse long-term outcome of diabetic patients after renal transplantation. 

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Clinical Nephrology, Volume 61, No. 4/2004 (253-260)

PTH secretion in patients with chronic renal failure assessed by a modified CiCa clamp method: effects of 1-year calcitriol therapy 

S. Schindler¹, M. Mannstadt², P. Urena³, G.V. Segre⁴ and G. Stein¹ 

¹Department of Internal Medicine III, University of Jena, ²Department of Internal Medicine, University of Munich, Germany, ³Clinique de l’Orangerie, Aubervilliers and INSERM Unit 349, Lariboisiere Hospital, Paris, France, and ⁴Endocrine Unit, Massachusetts General Hospital, Boston, USA 

Background: Secondary hyperparathyroidism (2 °HPT) in patients with chronic renal failure (CRF) is characterized by parathyroid gland hyperplasia and an intrinsic defect in the recognition of parathyroid hormone (PTH) secretion. Conflicting results have been reported regarding the set point for calcium-regulated PTH release and its modification by calcitriol therapy in hemodialysis patients. Additionally, the effect of calcitriol on the calcium/PTH relationship in predialysis CRF patients with early 2 °HPT has not been investigated. Our objective in this controlled study was to investigate the calcium/PTH relationship and to determine the calcium set point in patients with early stages of CRF before and after a 1-year treatment with calcitriol and in normal volunteers. Methods: Nine patients with an early stage of CRF (GFR between 20 and 50 ml/min × 1.73 m² b.s.) aged 35 – 77 years and 13 healthy volunteers (HV) aged 26 – 60, years were included in the study. All participants were investigated by sequential lowering and raising of serum calcium levels comprising the following phases: blood-ionized calcium (Ca²⁺) was lowered by about 0.2 mmol/l (3 steps), steady-state hypocalcemia of Ca²⁺ 0.2 mmol/l below the baseline (step 4), stop of the infusion for 5 minutes (step 5), Ca²⁺ was raised to about 0.2 mmol/l above baseline (steps 6 and 7), and a steady state hypercalcemia of Ca²⁺ 0.2 mmol/l above baseline (step 8). Ionized calcium and intact PTH (iPTH) were measured at 30 time points during 240 minutes. The calcium set point was determined using the classical 4-parameter model. The CiCa clamp test was performed before and after a 1-year treatment with 0.5 mg of calcitriol thrice weekly. Results: No differences in the set point were observed between HV and CRF patients with early 2 °HPT. Four of 9 patients responded to calcitriol treatment with a decrease in basal serum iPTH levels (“responders”). There was no difference between renal function (GFR 18 ± 6 vs. 17 ± 8 ml/min × 1.73 m² b.s.), set point (Ca²⁺ 1.07 ± 0.13 vs. 1.07 ± 0.06 mmol/l) and suppressibility of PTH secretion (PTH_min% 7.3 ± 1.6 vs. 8.2 ± 2.9) in responders vs non-responders, nor did these values change after treatment with calcitriol. PTH_min% decreased significantly in the whole group after treatment (10.4 ± 8.5 vs. 7.8 ± 2.4). Conclusions: Although the calcium set point was not different in predialysis CRF patients with early 2 °HPT compared to HV, calcitriol treatment improved the calcium-related suppression of PTH secretion (PTH_min%). 

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Clinical Nephrology, Volume 61, No. 4/2004 (261-274)

The effect of an exercise program during hemodialysis on dialysis efficacy, blood pressure and quality of life in end-stage renal disease (ESRD) patients 

T.L. Parsons¹, E.B. Toffelmire² and C.E. King-VanVlack¹ 

¹School of Rehabilitation Therapy, and ²Division of Nephrology, Department of Medicine, Faculty of Health Sciences, Queen’s University, Kingston, ON, Canada 

 Aim: We wished to determine if an 8-week program of exercise during dialysis in end-stage renal disease (ESRD) patients would increase urea removal (enhance dialysis efficacy) with subsequent improvements in work performance and perception of quality of life, and/or alterations in cardiovascular status. Methods: Self-care hemodialysis patients (EX, n = 6) performed cycle ergometry exercise 3 times per week during their dialysis session at 40 – 50% maximal work capacity for 15 min during each of the first 3 hours of dialysis and were matched for age, protein catabolism rate, and WL_max with a CON group (n = 7). Dialysis efficacy was measured using serum urea clearance (Kt/V) and dialysate urea clearance (DUC) during the first 2 hours of dialysis. Resting blood pressure was monitored on a sessional basis, pre- and postdialysis and during exercise in the EX group. QOL, measured using the SF-36 questionnaire, and WL_max were determined prior to and at 4 and 8 weeks of the exercise program. Results: DUC was significantly elevated in the EX group at the end of the exercise program, but was of insufficient magnitude to result in an overall increase in Kt/V. DUC decreased in the CON group but Kt/V remained unchanged. No changes in resting blood pressure occurred in either group over the course of the study, however, pulse pressure tended to increase in the CON group but decrease in the EX group, indicating a potential beneficial adaptation of the cardiovascular system in patients undergoing an exercise program. The exercise program had no effect on QOL scores and this was most likely due to the short duration of the exercise program and high-functioning level of the population studied as compared to normative data for this patient population. We also found that 33% of the exercise sessions in the 3rd hour of dialysis were not performed due to hypotensive events. Conclusion: Exercise during dialysis enhanced dialysate urea removal but not serum urea clearance. Alterations in the modality and the timing of exercise during dialysis may be required to elicit increases in serum urea clearance. It is also recommended that exercise during dialysis be performed during the first 2 hours of dialysis.  

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Clinical Nephrology, Volume 61, No. 4/2004 (278-281)

Postinfectious diffuse proliferative glomerulonephritis and acute renal failure in an HIV patient 

R. Enríquez¹, J.B. Cabezuelo¹, C. Escolano², M. Pérez³, F. Amorós¹,
F. Gutiérrez-Rodero² and A. Reyes¹

¹Nephrology Section, ²Infectious Diseases Unit, and
³Pathology Section, General Hospital of Elche, Spain 

Postinfectious proliferative glomerulonephritis may occur in HIV-infected patients, although it is not a common cause of severe acute renal failure in them. We report a woman with HIV infection, who developed hypocomplementemic acute nephritic syndrome 10 days after an upper respiratory infection. Systemic diseases were excluded. The serum creatinine level increased to 6.6 mg/dl. Renal biopsy showed diffuse endocapillary proliferative glomerulonephritis, with mesangial and capillary walls, granular deposits of IgG and C3 by immunofluorescence. She was given corticosteroids with progressive normalization of her renal function. No opportunistic infections have occurred during 1-year follow-up.   

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Clinical Nephrology, Volume 61, No. 4/2004 (282-288)

An atypical course of Caroli’s Disease in a renal transplant patient – case report and review of the literature 

S. Abouchacra¹, S. Toumeh¹, Y. Boobes¹, B. Bernieh¹ and W. Gorka² 

Departments of ¹Nephrology and ²Radiology, Tawam Hospital, Al-Ain,
Abu Dhabi, UAE 

This is a rare case of Caroli’s disease, diagnosed following renal transplantation in a patient with autosomal recessive polycystic kidneys. Despite advanced cystic transformation of the biliary tree with striking architectural changes, there was no evidence of portal hypertension or hepatic fibrosis. Moreover, the patient did not suffer a single episode of cholangitis, a most interesting feature of this case. Her clinical course was punctuated by repeated episodes of gastrointestinal and urinary tract infections with resistant organisms; but fortunately, she had no evidence of septicemia. Recurrent Salmonella gastroenteritis indicated a chronic carrier state with the dilated bile ducts possibly acting as a potential reservoir. This has significant implications considering the immune suppression associated with renal transplantation. In general, Caroli’s disease is rare. Therefore, a high index of suspicion for the diagnosis of Caroli’s disease is warranted especially in patients with ARPKD or ADPKD. Once confirmed, affected patients with end-stage renal disease such as our patient, should ideally undergo combined liver-kidney transplantation. 

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Clinical Nephrology, Volume 61, No. 4/2004 (289-294)

Brown tumors developing in renal transplant recipients with persistent hyperparathyroidism: 2 case reports and review of literature 

S. Lee¹, D.B. Lerer², H.D. Dorfman³ and M. Coco¹ 

¹Department of Medicine, Renal Division, ²Department of Radiology, and ³Department of Orthopedic Surgery, Orthopedic Pathology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York, USA 

Background: Brown tumors, evidence for severe hyperparathyroidism, are rare in end-stage renal disease, and are distinctly uncommon in patients with a functioning renal transplant. Case reports: We report 2 cases of brown tumors developing after renal transplantation, and discuss their presentation and treatment. We review the literature. Conclusions: We suggest that persistent hyperparathyroidism post-renal transplant requires aggressive intervention to avoid significant consequences. 

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