The clinical manifestations and response to treatment in South Africans with lupus nephritis.

There are varying observations on the influence of ethnicity on the clinical spectrum and response to treatment in lupus nephritis (LN). We studied a multiethnic South African LN cohort to determine the clinical manifestations, histological involvement and response to therapy. We reviewed the records of LN patients at Inkosi Albert Luthuli Central Hospital in Durban. There were 105 patients, 92.5% females and they comprised 49.1% Indians and 45.3% African Blacks. The mean age was 31.3 ± 12.5 years, and 41.5% had LN at first presentation of lupus. The most common histological classes were Class V alone in 34.9%, Class IV (± Class V) in 25.5% and Class III (±Class V) in 22.6%. The estimated glomerular filtration rate was reduced (<30 ml/min) at presentation in 15 (14.2%). Eighty-seven patients received therapy for LN. A response to induction therapy was noted in 81.6% and maintenance therapy (12 months) in 73.6%. Response to mycophenolate mofetil (MMF) was 80.4% and 68.4% during induction and maintenance therapy, respectively. There was no ethnic difference in the histological class or response to MMF but African Blacks had more severe renal disease at presentation. In conclusion, our multiethnic LN cohort shows a high prevalence of membranous LN and good response to treatment.

Statin therapy ameliorates renal allograft function.

BACKGROUND: Statins have proven ability as antilipidemic agents and benefit cardiovascular survival in transplant recipients. The pleiotropic effects of statins on renal function in renal allograft recipients are still undetermined. METHODS: Statin therapy was initiated according to guidelines for cardiovascular protection. Serum creatinine concentration and estimated glomerular filtration rate (eGFR) were analyzed before and after introduction of statins. The 73 patients who were retrospectively studied included those who were dialysis-dependent. Mean changes in eGFR and lipid profile were compared before and after commencing statins using chi(2) tests. RESULTS: Mean serum creatinine concentration 18 months before starting statin therapy was 160.13 mumol/L, and 24 months after starting statin therapy was 172.22 mumol/L. Mean eGFR was 53.40 mL/min 18 months before starting statin therapy, and decreased to 49.43 mL/min after starting statin therapy. This represented a decline in renal function of 0.22 mL/min/mo over 18 months. The eGFR at 12 months after beginning statin therapy was 52.67 mL/min, and at 24 months was 49.06 mL/min. The rate of decline of eGFR after starting statin therapy was significantly lower: 0.02 mL/min/mo over 24 months (P < .001). Total cholesterol and low-density lipoprotein cholesterol concentrations were significantly decreased after starting statin therapy (P < .001). Four of 73 patients developed graft failure within 24 months. CONCLUSION: Statin therapy in our setting was associated with a lower rate of decline in renal function in renal allograft recipients within 2 years of starting treatment.

A cross-sectional study of HIV-seropositive patients with varying degrees of proteinuria in South Africa.

Human immunodeficiency virus (HIV)-associated nephropathy (HIVAN) is the most common finding on renal biopsy in HIV-infected black patients and is also the commonest cause of end-stage renal disease in these patients. Early detection of HIVAN may be beneficial in evaluating early treatment. This study examined the pattern of renal diseases in HIV-infected South Africans and also attempted to diagnose HIVAN at an early stage. In this single-center cross-sectional study, 615 HIV-infected patients were screened for proteinuria. Thirty patients with varying degrees of proteinuria underwent renal biopsy. Patients with diabetes mellitus, uncontrolled hypertension, known causes of chronic kidney disease, and serum creatinine above 250 mumol/l were excluded. Patients in this study were not on antiretroviral therapy. HIVAN was found in 25 (83%) patients. Six of them (24%) had microalbuminuria. Altogether, seven patients with persistent microalbuminuria were biopsied and six (86%) showed HIVAN. Other biopsy findings included membranoproliferative nephropathy in two (7%) and interstitial nephritis in three (10%). Four patients with HIVAN had associated membranous nephropathy. HIVAN is the commonest biopsy finding among our study patients with HIV infection who present with varying degrees of proteinuria. Microalbuminuria is a manifestation of HIVAN in our study patients. Therefore, microalbuminuria may be an early marker of HIVAN, and screening for its presence may be beneficial. Renal biopsy may be considered in seropositive patients who present with persistent microalbuminuria, especially with low CD4 counts irrespective of good renal function. This will allow diagnosis and treatment of HIVAN at an early stage and may prevent further disease progression.

Liver cysts in Congolese patients with autosomal dominant polycystic kidney disease follow a family pattern.

BACKGROUND: It is now well established that at least two genes are associated with autosomal dominant polycystic kidney disease (ADPKD). OBJECTIVE: To analyse the clinical expression of ADPKD in Congolese patients and to compare ADPKD expression between families. METHODS: Following informed consent, ADPKD patients admitted to Brazzaville University Hospital (Congo) were reviewed and their relatives aged 20 years and older were screened by means of a clinical examination, abdominal ultrasound, urinalysis and determination of serum creatinine. RESULTS: We found 7 patients with ADPKD, belonging to 7 distinct families, and identified 100 relatives of whom 50, aged from 20 to 68 years, were diagnosed as having ADPKD. Polycystic kidney disease was associated with polycystic liver in 4 families. In the remaining 3 families no liver cysts were found. No family had a mixture of members with kidney cysts only and members with kidney and liver cysts. This finding was age-independent. CONCLUSION: Liver cysts follow a family pattern in our ADPKD patients. We suggest that our patients may carry at least two different genes for ADPKD, one of which may be associated with renal cysts alone and other with both renal and liver cysts.

Etiology and outcome of acute renal failure in children in congo-brazzaville.

Acute renal failure (ARF) is a common problem in the Congo. This is a six-year retrospective study aiming at analyzing the etiology and the outcome of ARF at the Brazzaville's University Hospital from 1989 through 1994. One hundred and five cases of ARF (0.99%), including 54 boys (51.4%) and 51 girls (48.6%), out of 10,512 children admitted in the department of Pediatrics have been recorded. ARF represented 13.09% of the causes in 802 patients with renal disorder. The main etiologies of ARF included acute gastroenteritis with dehydration (25.7%), nephrotic syndrome (14.7%), sepsis (15.23%), malaria (12.38%), and acute glomerulonephritis (9.5%). Most cases were managed conservatively, while peritoneal dialysis (PD) was used in eight cases (7.62%). The outcome of ARF was recovery in 50.5 %, death in 37 % and chronic renal failure in 12.5% of cases. Preventive measures may help in reducing the high mortality rate and the need for dialysis.

Failure of a daily haemofiltration programme using a highly permeable membrane to return beta 2-microglobulin concentrations to normal in haemodialysis patients.

In an attempt to return to normal serum beta 2-microglobulin levels in a group of seven ESRD patients, a programme of daily HF with highly permeable AN69 membranes was undertaken. Pre-HF beta 2-M serum levels stabilized after 4 days at 20 mg/l, only 40% lower than the initial concentration. A total of 985 +/- 20 mg beta 2-M was removed over the week. The beta 2-M release rate averaged 97 micrograms/min with a broad range of values (63-128 micrograms/min). beta 2-M release peaked at 602 micrograms/min 1 h after the end of the HF session before returning to baseline by 12 h post-HF. We conclude that a return to normal blood beta 2-M concentrations in ESRD patients seems quite unrealistic despite a highly intensive extracorporeal therapy. Therefore other therapeutic alternatives have to be designed to prevent or cure beta 2-M amyloidosis.

A study of beta 2-microglobulin skin deposits in dialyzed patients and healthy controls.

This study reports on beta 2-microglobulin (beta 2M) deposits in the skin of 12 uremic patients and three kidney transplant recipients compared with eight healthy controls. Uremic patients were treated by hemodialysis (HD), hemofiltration (HF), hemodiafiltration (HDF), or continuous ambulatory peritoneal dialysis (CAPD) for a period lasting from 1 to 19 years. Congo red staining of the skin was negative in patients and controls. However, immunofluorescent staining with an anti-beta 2-microglobulin monoclonal antibody was positive in the skin of all patients and of six of the eight controls. Beta 2M skin deposition is more intense in patients than in controls and increases with patient age and the duration of dialysis. A stron correlation is observed between the extent of skin beta 2M deposits and clinical manifestations due to beta 2M deposits in internal organs. However, no correlation is found between beta 2M skin deposits and sex or beta 2M serum levels.

Clinical and microbiological evaluation of a postdilutional hemofiltration system with in-line production of substitution fluid.

Safety and efficacy of a recently developed hemofiltration (HF) system with in-line production of substitution fluid (GHS-10; Gambro, Lund, Sweden) based on a sterilizing filtration of acetate buffered dialysate has been evaluated in 4 patients over a 6-month period. Two patients were prematurely excluded from the study: 1 because of acetate intolerance and the other because of kidney transplantation. Two patients completed the study (240 HF sessions). Treatment adequacy was maintained in the 2 medium term treated patients according to the usual clinical and biochemical criteria and a mean exchange volume of 100-105 liters/week (30-35 liters/session three times weekly). Urea kinetic modeling analysis performed over all HF cycles gave the following results: dialysis index (urea clearance.time-on HF/urea volume space) (KT/V) approximately 1-1.1, urea time averaged concentration (UREA TAC) approximately 15-20 mmol/l, and protein catabolic rate (PCR) approximately 1.1-1.2 g/kg/day. Rare clinical adverse symptoms observed during the course of sessions were attributed to acetate intolerance. Microbiological safety was confirmed in vivo by the absence of pyrogenic reactions after 240 HF sessions (approximately 7 m3 substitution fluid infused intravenously) and in vitro by the constant absence of bacteria and/or endotoxin content limulus amaebocyte lysate (LAL) sensibility threshold 10 pg/l within the infusate produced during the sham HF sessions. The fluid mass balance obtained with the GHS-10 monitor was excellent. The electrolyte composition as judged by Na variation remained in a range of 2-3%. GHS-10 used in this study for postdilutional HF confirms that a large quantity of intravenous quality fluid may be safely produced by ultrafiltration from dialysate. It also introduced a new dimension in biocompatibility of dialysis by demonstrating that sterile dialysate may be routinely produced and used for routine dialysis.

Beta-2 microglobulin serum levels in maintenance dialysis. What does it mean?

beta-2 Microglobulin levels (beta-2M) were analyzed at four month intervals in sera of 237 patients on various forms of dialysis over a 2 year period; twelve patients volunteered to participate in short-term kinetics studies. Duplicate beta-2M measurements in biologic fluids were performed using an RIA kit. The data presented confirm elevated serum beta-2M in dialyzed patients whatever the dialysis method used and give an overview on various factors affecting circulating serum beta-2M. Intraindividual beta-2M variations were 13% in stable ESRD patients. Unusually high values (greater than 2 SE) were observed in patients presenting with severe intercurrent disease (e.g., cancer). The only significant difference observed between groups of patients, HD (46 +/- 1 mg/L) and PD (IPD: 33 +/- 3, CAPD: 37 +/- 2 mg/L), was due to the residual renal function preserved in a higher percentage of PD patients. No significant difference was noted in HF (40 +/- 2 mg/L) and HDF (38 +/- 5 mg/L) patients, despite a higher beta-2M removal rate. beta-2M membrane permeability differs greatly among filters. It is high for AN69 and Polysulfone, intermediate for Polyamide, low for Polyacrylonitrile and none for Cuprophane. Peritoneal membrane is highly permeable to beta-2M with beta-2M dialysate/serum levels of 0.20 at the end of a 6 hr exchange. In conclusion, beta-2M determination in uremic patients is useful in assessing material permeability and biocompatibility. However, it is too early to determine the impact or the beneficial effects of using highly permeable membrane to prevent beta-2M-amyloidosis related nonarticular complications.

[What does circulating beta 2 microglobulin signify in uremic patients on maintenance dialysis?]. / Que signifie la beta 2 microglobuline circulante chez les urémiques en traitement de suppléance?

The authors report a 2 years prospective study on s beta 2M variations observed in a large uremic population (237 patients, 159 M, 78 F, age: 51.1 +/- 5.9 y.o.). The study consisted in two parts. A long term follow-up of s beta 2M in patients regularly treated with various dialysis modalities; hemodialysis (HD), hemofiltration (HF), hemodiafiltration (HDF), intermittent peritoneal dialysis (IPD) and continuous ambulatory peritoneal dialysis (CAPD). s beta 2M was found elevated in the overall population (41.4 +/- 10.2 mg/l) with a 12.5% variation over time observation in stable patients, not influenced by sex, causal nephropathy, and dialysis mode in anuric patients, beta 2M was inversely correlated with residual diuresis. Residual kidney function preserved longer and in a higher proportion of PD patients was the only significant fact explaining for the difference observed in s beta 2M levels between HD (46 +/- 5) and PD (33 +/- 3) patients. Intercurrent inflammatory and tumoral states increased significantly s beta 2M level in uremic patients. The short term study showed that highly permeable membranes (AN69, polysulphone) used either in HD, HF or HDF were able to decrease s beta 2M from 50 to 60%, and to remove 150 to 200 mg per session, while on the opposite HD/cuprophane increased s beta 2M from 10 to 15%. beta 2M dialysate/plasma equilibrium ratio for peritoneal membrane after a 6 hour dwelling time was 0.20, permitting a net removal of 45 +/- 4 mg/24 h.(ABSTRACT TRUNCATED AT 250 WORDS)