Parathyroid carcinoma secondary to prolonged hyperplasia in chronic renal failure and in coeliac disease.

The presentation of parathyroid carcinoma in patients with chronic renal failure is rare, although with improvements in life expectancy associated with this condition there have now been 12 reported cases, including the first case we report here. It has been proposed that in these cases there has been a malignant transformation of benign parathyroid hyperplastic tissue. We also report the first case of parathyroid carcinoma associated with coeliac disease and suggest that the same mechanism may be responsible. We review the presentation, diagnosis, treatment and natural history of the disease.

A controlled trial of two bicarbonate-containing dialysis fluids for CAPD--final report.

BACKGROUND: The combination of a low pH and a high concentration of lactate which is present in most dialysis fluids is found to be cytotoxic in vitro. For these reasons it would seem logical to use a bicarbonate-containing solution and thus automatically provide a solution with a neutral pH. METHODS: A parallel, randomized, open-label, prospective 2-month trial with an optional 4 month extension was undertaken to compare two novel bicarbonate-based solutions; one containing 38 mmol/l of bicarbonate (B), and one containing a mixture of 25 mmol/l bicarbonate and 15 mmol/l of lactate (B/L), with a control solution (C) containing 40 mmol/l lactate. RESULTS: Three groups of 19 (C), 20 (B), and 20 (B/L) patients were recruited and data from approximately 55 patient months were accumulated in each group. The data show that both bicarbonate-based solutions maintain acid-base levels within the normal range, that there were no changes in any of the other blood biochemistry parameters measured in the peritoneal equilibration test or with regard to adequacy of dialysis, and that furthermore, both solutions were well tolerated. CONCLUSIONS: This study showed that either the bicarbonate or bicarbonate/lactate solutions could be utilized efficaciously in patients undergoing CAPD.

Presymptomatic detection of familial juvenile hyperuricaemic nephropathy in children.

We studied 34 apparently healthy children and 2 propositi from kindreds with familial juvenile hyperuricaemic nephropathy (FJHN) - a disorder characterised by early onset, hyperuricaemia, gout, familial renal disease and a similarly low urate clearance relative to glomerular filtration rate (GFR) [fractional excretion of uric acid (FEur) 5.1+/-1.6%] in young men and women. In addition to the propositi, 17 asymptomatic children were hyperuricaemic -- mean plasma urate (368+/-30 micromol/l), twice that of controls (154+/-41 micromol/l). Eight of them had a normal GFR ( > 80 ml/min per 1.73 m2), and 11 renal dysfunction, which was severe in 5. The FEur in the 14 hyperuricaemic children with a GFR > 50 ml/min was 5.0+/-0.5% and in the 5 with a GFR < or =50 ml/min was still low (11.5+/-0.2%) compared with controls (18.4+/-5.1%). The 17 normouricaemic children (185+/-37 micromol/l) had a normal GFR (>80 ml/min) and FEur (14.0+/-5.3%). The results highlight the dominant inheritance, absence of the usual child/adult difference in FEur in FJHN and presence of hyperuricaemia without renal disease in 42% of affected children, but not vice versa. Since early allopurinol treatment may retard progression to end-stage renal failure, screening of all relatives in FJHN kindreds is essential.

Contribution of individual drugs to gingival overgrowth in adult and juvenile renal transplant patients treated with multiple therapy.

Drug regimens for transplantation often consist of multiple therapeutic agents and may result in drug-induced gingival overgrowth (DIGO). The aim of this study was to investigate the contribution of individual drugs in renal transplant patients. 147 adults (19-84 years) and 60 juveniles (3-18 years) were scored for DIGO and other clinical variables. Duration of treatment, dosage of drugs per kg body weight and serum cyclosporin levels were recorded. 44% of adults and 27% of children had DIGO. All patients were receiving prednisolone. More adults than children were administered cyclosporin, the reverse was true of azathioprine (p<0.01). Explanatory models were evaluated by stepwise ordinal polynomial logistic regression. Statistically significant explanation (p<0.05) of DIGO was afforded by prednisolone, nifedipine and azathioprine concentrations in adults and by cyclosporin, nifedipine and azathioprine concentrations in juveniles. Prednisolone and azathioprine were inversely related to the degree of DIGO. Plaque and irregularity scores, lip coverage and mouthbreathing status showed significant additional explanation in adults, replacing nifedipine and azathioprine in the final model. Irregularity was additionally explanatory in children, but no other clinical variables. A larger proportion of the variance of DIGO was explained by the available variables in children than in adults (pseudo r2=0.50 versus 0.25). The degree of DIGO in renal transplant patients is influenced by the dosage of a number of individual components of multiple drug therapy independently of the presence of local clinical factors.

Long-term follow-up after total parathyroidectomy without parathyroid reimplantation in chronic renal failure.

Forty-three patients with secondary or autonomous hyperparathyroidism complicating chronic renal failure (CRF) underwent total parathyroidectomy (PTX) (follow-up 2-18 years, mean 8.7 years). Five were on conservative treatment for CRF, 35 on regular dialysis, and only three had a functioning allograft. At PTX, the most frequent findings were uncontrollable hypercalcaemia, musculo-skeletal pain, radiographic changes in the phalanges, and raised plasma parathyroid hormone (PTH) concentration. Pre-operatively, all patients were loaded with dihydrotachysterol or 1-alpha-OH cholecalciferol. Postoperatively, they were maintained on tapering doses of the same drugs and, briefly, oral calcium supplements. Five glands were identified and removed in two patients, four in 35 patients, three in three patients and only two in one patient. All had changes of hyperplasia and adenoma formation, except for one with a parathyroid carcinoma. Prompt symptomatic and radiographic improvement occurred, with normalization of plasma calcium and alkaline phosphatase. Postoperative PTH levels were available in 33 patients (23 by intact PTH assay): they were persistently high in 10/33 (2/23 intact); normal in seven (6 intact); low in 11 (3 intact), and undetectable in four (3 intact). Thus, PTX was incomplete in the majority of patients. Following transplantation, 3/20 (3/18 intact) patients still had detectable PTH. Only one patient developed symptomatic recurrent parathyroid disease requiring re-operation, and complications were few. Small dosages of vitamin D continue to be required, but not calcium supplementation, and no clinical effects of possible adynamic bone have been noted. At later renal transplantation in 27 patients, an easily treatable, uncomplicated hypocalcaemia was noted in 33%.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute arsenic poisoning: absence of polyneuropathy after treatment with 2,3-dimercaptopropanesulphonate (DMPS).

Two men aged 19 and 21 years ingested 1 g and 4 g respectively from 3 kg of a white crystalline powder that they thought was a substance of abuse. It was later identified as almost pure arsenic trioxide. Both had nausea and vomiting and one developed acute renal failure. Each was treated with 2,3-dimercaptopropanesulphonate (DMPS), and made a full recovery with no evidence of prolonged renal or neurological impairment. The DMPS-arsenic complex is probably associated with lower penetration into the CNS and as a consequence treatment with DMPS may result in lower acute and chronic neurotoxicity than treatment with the currently standard recommended chelating agent dimercaprol (British Anti-Lewisite; BAL).

Immunohistochemical studies of the peritoneal membrane and infiltrating cells in normal subjects and in patients on CAPD.

We performed immunohistochemical studies on biopsies of the parietal peritoneal membrane of 33 subjects to investigate whether other cell populations, in addition to mononuclear cells free in the dialysate, might participate in the defense of the peritoneum against microbial invasion during CAPD. Leukocytes were found to concentrate in two areas: a submesothelial layer composed of elongated macrophages displaying activation and maturation markers, and perivascular, less mature macrophages closely associated with T cells and HLA-DR, ICAM-1 and VCAM-1 expressing endothelial cells. Normal mesothelial cells were found to express constitutively the transferrin receptor and the adhesion molecules ICAM-1 and VCAM-1 but not ELAM-1. There were no major differences between normal and uremic subjects, while peritoneal dialysis patients exhibited minor derangements of the submesothelial layer and slight up-regulation of the expression of HLA-DR on endothelial cells. Peritonitis was associated with increased submesothelial cellularity and, particularly, perivascular leukocyte infiltration accompanied by increased expression of HLA-DR and adhesion molecules. Besides mononuclear cells free in the dialysate, this study demonstrates the existence of two additional peritoneal membrane leukocyte populations: submesothelial macrophages, and perivascular macrophages and T cells. It also suggests the existence of a fourth population of intracavitary leukocytes adherent to mesothelial cells. Studies are now necessary to evaluate their exact role in the host defence against peritonitis during CAPD.

Percutaneous transluminal renal angioplasty in patients with renal failure.

Renovascular disease is a common cause of end-stage renal failure in the elderly population. We assessed the role of percutaneous transluminal renal angioplasty in the treatment of patients with renal failure due to renovascular disease by analysing our results in 60 patients treated between 1982 and 1991. All the patients had a baseline serum creatinine level greater than 150 mumol/l; improvement in renal function was defined as a 20 per cent reduction in this level. Seventy-five angioplasty procedures were attempted on 70 arteries in 60 patients. There was an improvement in renal function in 24 patients (40 per cent), whilst six (10 per cent) showed deterioration. The most dramatic improvement was seen in a small group of patients who had suffered an acute deterioration in renal function prior to angioplasty. There was a low incidence of serious complications. Renovascular disease is an important reversible cause of chronic renal failure and should be investigated aggressively so that percutaneous transluminal renal angioplasty can be undertaken in selected patients.

Peritoneal drainage: an important element in host defence against staphylococcal peritonitis in patients on CAPD.

The growth of Staphylococcus aureus and coagulase-negative staphylococci were studied in fresh and effluent peritoneal dialysate from patients on continuous ambulatory peritoneal dialysis (CAPD). Peritoneal drainage during CAPD removes bacterial contaminants from the peritoneal cavity with an efficiency that depends upon the volume of peritoneal fluid remaining after drainage (residual volume). Combination of our data on the growth of coagulase-negative staphylococci in dialysate with a mathematical model of peritoneal drainage during CAPD shows that a residual volume of less than 800 ml (normal = approximately 400 ml) will prevent survival in the peritoneal fluid. A residual volume of less than 200 ml is required to eliminate S. aureus because of its faster rate of growth in dialysate. Previous work has shown that numbers of macrophages are too few to influence bacterial growth in the peritoneal dialysate. Coagulase-negative staphylococci adhere poorly to mesothelial cells in culture. Survival within the peritoneal cavity during CAPD probably depends on colonization of the PD catheter. Coagulase-negative staphylococcal peritonitis is likely to be localized to areas of the peritoneal membrane in close contact with the PD catheter. S. aureus is able to multiply in the peritoneal dialysate during CAPD and thereby causes generalized peritonitis.

Familial juvenile gouty nephropathy with renal urate hypoexcretion preceding renal disease.

This paper reports investigations in a young woman with renal disease and six other seemingly healthy young members of a new kindred (four male:two female) with familial juvenile gouty nephropathy (McKusick 16200). The family had previously been known to have a "familial" renal disease, but came to attention through an isolated episode of gout in the propositus when renal function was already impaired. A reduced GFR was found in three of the other six subjects. Hyperuricemia associated with a grossly reduced fractional uric acid clearance (Cur/Ccr x 100) was present in the propositus and five kindred members, three of whom were children. The finding of this abnormality in two subjects with normal GFR suggests that this apparent hallmark of the disease precedes the onset of renal damage. The results confirm the dominant nature of the disorder, and highlight the need to investigate all kindred members of patients with juvenile gout and renal failure. Early recognition is important, since allopurinol therapy in doses adjusted to the reduced renal function may ameliorate the progression of the renal lesion.