GB virus C prevalence in blood donors and high risk groups for parenterally transmitted agents from Gauteng, South Africa.

The prevalence of GBV-C infection in voluntary blood donors and in groups at high risk for parenteral exposure to infectious agents was studied. The high risk groups included chronic renal failure patients on haemodialysis, renal transplant patients and haemophiliacs from Gauteng. The presence of GBV-C RNA in these populations was determined using reverse transcription polymerase chain reaction (RT-PCR) in the 5' non-coding region (NCR) of the virus. Of the blood donors, 11.1% (95% CI 7.6, 15.8) were positive, whereas 23.8% (95% CI 12.6, 40.2) of haemodialysis patients and 23.5% (95% CI 15.9, 33.3) of the haemophiliacs were infected with GBV-C. The highest proportion of infection was in the renal transplant patients, where 41.2% (95% CI 35.1, 47.7) were found to have circulating GBV-C RNA. Serological markers for hepatitis B (HBV) and hepatitis C viruses (HCV) were also measured as indicators of other hepatitis viruses with important parenteral transmission routes. Of the GBV-C positive blood donors, 3.6% were also HBsAg positive and none were positive for HCV. The GBV-C positive patients on haemodialysis were not positive for either HBsAg or antibodies to HCV, but had evidence of past infection with HBV since 40% were anti-HBc positive. The greatest proportion of HCV positives was in the haemophiliac group, 91.3%, none of these were HBsAg positive but 39.1% had anti-HBc. In the GBV-C positive renal transplant patients, 4% had HBsAg, 13.3% had anti-HBc and 2.1% had antibodies to HCV. This is the first report describing the prevalence of GBV-C in South African populations.

Kaposi's sarcoma-associated herpesvirus in Kaposi's sarcoma occurring in immunosuppressed renal transplant recipients.

Kaposi's sarcoma-associated herpesvirus (KSHV) has been implicated in the genesis of Kaposi's sarcoma and other tumors occurring in immunosuppressed individuals. Using amplification by the polymerase chain reaction and nucleotide sequencing of extracted DNA, we have detected the KS330(233) sequence of KSHV DNA in Kaposi's sarcoma tissue from 4 immunosuppressed renal transplant recipients. The sequences shared a greater than 98% homology with those described in KSHV DNA from Kaposi's sarcoma in patients with acquired immunodeficiency syndrome. In another 2 renal transplant recipients KSHV DNA could not be detected in scar tissue at the site of previous Kaposi's sarcoma that had resolved after immunosuppression was discontinued and haemodialysis recommenced. These findings support the hypothesis that KSHV may be the infectious agent concerned in the genesis of Kaposi's sarcoma.

Indapamide (Natrilix): the agent of choice in the treatment of recurrent renal calculi associated with idiopathic hypercalciuria.

OBJECTIVE: To compare the hypocalciuric and potential side-effects of hydrochlorothiazide (HCT) to indapamide (IND; a thiazide-like drug) in patients with idiopathic hypercalciuria. PATIENTS, SUBJECTS AND METHODS: Twelve patients with recurrent renal calculi and renal hypercalciuria were studied using a randomized double-blind cross-over protocol. In addition, because the side-effects of HCT are attenuated using small doses, the hypocalciuric effect of 12.5, 25 and 50 mg daily was assessed in six normal subjects. RESULTS: There was a significant reduction in urinary calcium excretion using both agents, with a mean (SD) of 6.06 (2.68) and 3.37 (2.00) mmol/24 h using IND, and 5.58 (1.98) and 3.93 (2.35) mmol/24 h using HCT, before and after treatment (P < 0.05). The treatment was not sufficiently prolonged to assess adequately all the side-effects of either agent but both produced a similar decrease in serum potassium, whilst HCT significantly increased the mean (SD) serum urate levels, from 0.34 (0.09) to 0.43 (0.08) mmol/L (P < 0.01). There was also a significant decrease in mean (SD) urinary citrate excretion in those receiving HCT, from 1.41 (1.05) to 1.00 (0.71) mmol/24 h (P < 0.001), but not in those receiving IND, from 1.19 (0.71) to 1.18 (0.79) mmol/24 h. Although there was a hypocalciuric effect with doses of 12.5 and 25 mg HCT, it was sub-therapeutic when compared with the dose of 50 mg. CONCLUSION: At a daily dose of 2.5 mg, IND is at least as effective as 50 mg HCT in controlling hypercalciuria. Because of its safety profile and lack of effects on urinary citrate excretion, this agent should be the preferred therapy for patients with idiopathic hypercalciuria and recurrent renal calculi.

Long-term effects of potassium citrate therapy on the formation of new stones in groups of recurrent stone formers with hypocitraturia.

OBJECTIVE: To compare stone formation rates before (as total rates and during remote periods) and after therapy with potassium citrate in patients with hypocitraturia. PATIENTS AND METHODS: The study comprised 15 patients with hypocitraturia only (Group I) and 12 patients with hypocitraturia associated with other abnormalities (Group II), all of whom were recurrent stone formers. Their urine chemistry, including citrate, was measured before and after treatment. RESULTS: In both groups, the urinary citrate concentration increased significantly to within normal limits during therapy with potassium citrate (P < 0.005). The rate of total stone formation in patients in Group I decreased significantly from 0.7/year before to 0.13/year after treatment (P < 0.005). The corresponding remote stone formation rate before (0.88/year) was significantly greater than the rate after treatment (0.13/year; P < 0.005; follow-up 4.6 +/- 1.9 years). Patients in Group II showed a similar striking decrease in total stone formation rate, from 1.2/year to 0.08/year after treatment (P < 0.005). The corresponding remote stone formation rate (1.66/year) before was significantly greater than that after treatment (0.08/year; P < 0.005; follow-up 4.1 +/- 1.6 years). There was a remission rate of 93% for stone formation over the complete follow-up. CONCLUSION: Potassium citrate appears to be the drug of choice in the long-term treatment of patients with hypocitraturia as it not only decreases the rate of stone formation but also maintains normal citrate levels in the urine.

Variants of Kaposi's sarcoma in Southern Africa. A retrospective analysis (1980-1992).

All types of Kaposi's sarcoma (KS) are represented in the Southern African region. We present a retrospective analysis of patients with KS, treated and followed up at the Johannesburg General Hospital over a 12-year period (1980-1992). One hundred and nineteen patients with KS, divided into four groups according to their etiology (classical; endemic African; renal transplant recipients; epidemic AIDS-related) were analyzed. Choice of treatment (radiotherapy or chemotherapy) was individualized and based on clinical criteria, extent of disease and severity of symptoms. Kaposi's sarcoma showed a very high response rate to radiation therapy, regardless of variant, radiation modality or schedule. Chemotherapy was also effective in the more aggressive pattern of endemic African KS. Epidemic Kaposi's sarcoma showed the same poor outcome as demonstrated by its Western counterpart. We conclude that radiation therapy can provide excellent palliation with only minimal side-effects in all variants of KS seen in Southern Africa.

PIP: During 1980-92, in South Africa, the Department of Medical Oncology and Clinical Hematology of Johannesburg General Hospital received 119 patients aged 23-82 with histologically confirmed Kaposi's sarcoma (KS). Researchers divided them into four groups based on their etiology: classical KS, endemic African KS, renal transplant recipients, and epidemic AIDS-related KS. The oncologists determined the treatment for each individual based on clinical criteria, extent of disease, and severity of symptoms. Regardless of type of KS, radiation modality, or schedule, KS responded very well to radiation therapy (e.g., partial or complete remission: 86% for endemic African KS, 90% for AIDS-related KS [partial remission only]). Radiation therapy was more likely to provide symptomatic relief for AIDS-related KS patients than chemotherapy (80% vs. 9%). Among AIDS-related KS patients, all nonresponders died rapidly from progressive disease and/or from exacerbating opportunistic infections. Chemotherapy also effectively treated endemic African KS (partial or complete remission: 81% vs. 38% for AIDS-related KS). Side effects were minimal in KS patients being treated with radiation. In conclusion, radiation therapy provides excellent results with few side effects in all types of KS in South Africa.

Hereditary interstitial nephritis without basement membrane changes.

Hereditary interstitial nephritides are a heterogeneous group of disorders comprising medullary cystic disease, several varieties of Alport's syndrome and also one familial disorder with a distinct clinical syndrome and without characteristic ultrastructural glomerular basement membrane changes. Our family consisted of 11 members, 5 of which presented with renal dysfunction of varying degrees. Clinically, the affected siblings presented with long-standing hypertension, minimal proteinuria and no hematuria. All known causes of a secondary diffuse interstitial nephritis, Alport's syndrome and medullary cystic disease have been excluded. An HLA association is suggested between the affected and unaffected members of the family. Renal biopsy subsequently showed the typical features of a chronic interstitial nephritis without basement membrane changes.

Renal allograft preservation: a comparison of University of Wisconsin solution and of hypothermic continuous pulsatile perfusion.

A study was performed to compare early allograft function in kidneys preserved with University of Wisconsin (UW) solution to kidneys preserved by hypothermic pulsatile perfusion. The study consisted of two sets of data. The first set was a donor-paired study (matched data) of 30 heart-beating, hemodynamically stable donors. After removal from the donor each cooled kidney was individually prepared for preservation. One kidney was flushed with +/- 500 ml of UW solution and stored in UW solution on slushed ice. The other kidney was continuously perfused with cooled (4-6 degrees C) cryoprecipitated plasma. The kidneys were transplanted into suitable recipients in a random sequence. Twelve donors were excluded from the study because one or both kidneys were transplanted into recipients who had previously been transplanted. The remaining 36 kidneys were implanted into two similar groups after a mean of 19 hours in the pulsatile perfusion group and 18 hours in the UW solution group. The second set of data consisted of all the kidneys preserved in UW solution (n = 62) at our institution and of 57 kidneys preserved by hypothermic continuous pulsatile perfusion during the same period (mixed data) and was used to evaluate the effect of prolonged preservation (longer than 24 hours) on delayed graft function. Both of these groups were also comparable. Acute tubular necrosis (ATN) was defined as the need for dialysis during the 1st week after transplantation, and delayed function as the delayed clearance of creatinine during the early post-operative phase.(ABSTRACT TRUNCATED AT 250 WORDS)

Kaposi's sarcoma in renal transplant recipients. Experience at Johannesburg Hospital, 1966-1989.

Between August 1966 and December 1989, 989 renal transplant recipients were followed up at the Renal Transplant Unit of Johannesburg Hospital. Seventy-five (7%) patients developed a total of 95 malignancies of which 5 (6%) were Kaposi's sarcoma. All patients received immunosuppressive agents; steroids, azathioprine and/or cyclosporin A. Clinical presentations included both limited skin involvement (1 patient) and disseminated forms of the disease: necrotic oral lesions (1 patient); disseminated skin involvement and lung metastases (1 patient); and widespread skin lesions with lymphadenopathy (2 patients). Four patients responded with complete tumour regression at all sites upon withdrawal of the immunosuppressive drugs. One patient suffered disease progression, and immunosuppression was continued, albeit at reduced dosages. These cases illustrate a relatively rare complication of immunosuppressive therapy. However, complete withdrawal of immunosuppressive drugs may result in sustained complete regression, despite the presence of advanced KS.

The effect of dopamine on graft function in patients undergoing renal transplantation.

We studied the effect of a low-dose dopamine infusion on graft function in 60 patients undergoing transplantation with cadaveric kidneys in a prospective controlled trial. Recipients were allocated to either a control or a dopamine group, the latter receiving a 3 micrograms.kg-1 x min-1 infusion of dopamine starting intraoperatively. Evaluation of dopamine's effect was undertaken in two stages, namely, (i) initial graft function 1 wk after transplantation and (ii) graft survival at 3 mo. Initial graft function was determined by the ability of the transplanted kidney to reduce serum creatinine, and the development of acute tubular necrosis as confirmed by renal biopsy. Of the dopamine group 33.3% developed acute tubular necrosis compared to 23.3% of the control group. The second-stage evaluation was based on plasma creatinine levels and the requirement for dialysis within 3 mo of transplantation. 92.8% of the dopamine group and 76.9% of the control group had good graft function. No statistically significant difference between the two groups was found. The perioperative infusion of dopamine at 3 micrograms.kg-1 x min-1 was not shown to have any beneficial effect on the transplanted kidney in patients who do not have serious vascular disease, or who do not receive kidneys subjected to prolonged hypotension or prolonged preservation or anastomotic times.

Adenine nucleotide concentrations and energy charge in muscle of chronic haemodialysis patients.

Adenine nucleotide concentrations and energy charge ratios were measured in muscle samples collected during transplant surgery of 7 patients suffering from chronic renal failure and undergoing haemodialysis. The energy charge ratio of 0.75 in the muscle of transplant patients was significantly lower (p less than 0.01) than that of 0.89 found in muscle from controls. The lower energy charge ratio and increased concentrations of adenosine diphosphate and adenosine monophosphate may contribute to the patients' reduced exercise ability and their poor metabolic state.

Hyperoxaluria in patients with recurrent calcium oxalate calculi: dietary and other risk factors.

The presence of mild hyperoxaluria in recurrent calcium oxalate stone formers is controversial. The aim of this study was to identify recurrent stone formers with mild hyperoxaluria and to classify them further by assessing their response to a low oxalate diet. In addition, the prevalence of other risk factors for stone formation in this group of patients was investigated. A total of 207 consecutive patients with recurrent renal calculi were screened and 40 (19%) were found to have mild hyperoxaluria. Of these, 18 (45%) responded to dietary oxalate restriction by normalising their urinary oxalate. The remaining 22 patients were classified as having idiopathic hyperoxaluria and were subdivided into those in whom urinary oxalate excretion was consistently elevated in all specimens measured and those in whom the elevation was intermittent in nature. Dietary oxalate restriction had a partially beneficial effect in lowering oxalate excretion in the patients with persistent hyperoxaluria. No difference in urinary oxalate excretion was found after dietary restriction in the patients with intermittent hyperoxaluria. Other risk factors, including dietary, absorptive and renal hypercalciuria and hypocitraturia, were documented, the prevalence of which (65%) was not significantly different from that (62.5%) found in 40 age- and sex-matched calcium stone formers without hyperoxaluria. The prevalence of hyperuricosuria was significantly greater in patients with hyperoxaluria when compared with stone controls. Further studies are required to elucidate the underlying mechanisms of hyperoxaluria in recurrent stone formers.

The relevance of more sensitive ancillary crossmatch techniques in predicting early cadaver renal graft outcome.

The predictive value of varying levels of antibody activity, its class and antigen specificity in sera of 81 recipients of cadaver renal allografts was evaluated. Recipients for transplantation were selected on the basis of a negative dye uptake T-cell crossmatch, after which the more sensitive 51Cr release technique was employed in a blind study using unseparated donor target cells. Recipient sera with peak panel reactivity and current samples were evaluated before and after reduction with dithiothreitol to destroy the IgM subclass. Double absorption with pooled platelets allowed antibodies against HLA class I antigens to be distinguished from those against HLA class II/non-HLA antigens. Optimal levels of cytotoxicity were established, giving a sensitivity of 73%. Data were assessed in terms of positive predictive value, and showed that conventional T-cell crossmatching is adequate for the primary transplant group, but more sensitive ancillary tests are indicated for regrafts. In this category of patients, IgG antibodies, whether against HLA class I antigens or HLA class II/non-HLA antigens, were highly predictive of early graft loss (positive predictive value 50%-100%). Using this protocol for patient selection, 1-month graft survival would have improved from 73% to 96%.

Chronic laxative abusers with pseudo-idiopathic oedema and autonomous pseudo-Bartter's syndrome. A spectrum of metabolic madness, or new lights on an old disease?

The numerous metabolic abnormalities encountered in chronic purgative abusers were investigated and the new concept of autonomous pseudo-Bartter's syndrome documented. Detailed metabolic screening tests were performed in 9 women aged 17-54 years. Two patients underwent further studies, including serum renin and aldosterone, blood volume, total body potassium, urinary chloride and prostaglandin determinations, and each underwent renal biopsy on admission and after 1 year free from laxative abuse. Clinical complications included confusion, convulsions, coma, skeletal muscle weakness with or without paralysis or rhabdomyolysis, cardiac failure, urinary tract infections and bone disease (osteomalacia, secondary hyperparathyroidism and osteoporosis). Hypokalaemia, hypomagnesaemia, hypocalcaemia and hypophosphataemia were frequent findings. Serum creatine kinase correlated inversely with the product of the potassium and serum phosphate (r = -0.86; P less than 0.03), suggesting that hypokalaemia and hypophosphataemia act synergistically to produce muscle damage. After laxative withdrawal, oedema and weight gain, followed by diuresis, ensued in 7 patients. In the other 2, ongoing chloruresis, kaliuresis, hyper-reninaemia and raised urinary prostaglandin secretion persisted. Renal biopsies in these 2 patients showed the features of juxtaglomerular apparatus hyperplasia as well as medullary interstitial cell hyperplasia. In conclusion, pseudo-Bartter's syndrome was documented in 9 chronic laxative abusers. Because patients often indulged in more than one aberrant habit, e.g. laxative and/or diuretic abuse or bulimia, the clinical syndrome produced a myriad of confounding metabolic derangements, which we termed 'metabolic madness'. Laxative withdrawal was complicated by temporary pseudo-idiopathic oedema, which persisted in 2 patients. Further studies in these 2 women strongly supported the concept of 'autonomous pseudo-Bartter's syndrome'.(ABSTRACT TRUNCATED AT 250 WORDS)

Microscopic polyarteritis--a treatable cause of rapidly progressive renal failure due to necrotising glomerulonephritis.

The clinical features of 25 patients with microscopic polyarteritis are reviewed. Major indications of disease were haematuria and proteinuria accompanied by significant renal dysfunction, which was rapidly progressive in the majority of patients. Unrewarding investigations aimed at defining a cause of haematuria that could be treated surgically only served to delay diagnosis, which could be promptly made by renal biopsy. Early institution of cyclophosphamide therapy led to ablation of the inflammatory process and stabilisation of renal function. In men, who were affected twice as often as women, there was a striking association with employment in the goldmining industry.