The perioperative challenge of nephrogenic diabetes insipidus: a multidisciplinary approach.

Nephrogenic Diabetes Insipidus (NDI) is characterised by the inability of the kidneys to concentrate urine in response to arginine vasopressin (AVP). Such patients typically experience polyuria and polydipsia because of this inability to autoregulate their water balance. This provides a perioperative challenge that could lead to a life-threatening situation. This article documents a patient with NDI who underwent an elective bowel re-anastomosis. Two peak serum sodium values were attained. The first when the patient was retaining sodium due to an inappropriate fluid regimen and the second due to hypovolaemia. The literature is reviewed and principles for NDI perioperative management are proposed.

Exercise during haemodialysis: West of Scotland pilot study.

BACKGROUND: Exercise during dialysis (EDD) in End-Stage Renal Disease (ESRD) has been documented as an effective intervention to improving a patient's aerobic capacity. AIMS: This pilot study aimed to confirm physiological improvements, to establish its safety and practicality and to form guidelines for a long-term study, leading to the integration of EDD in ESRD therapy. METHODS: A total of 17 patients on hospital haemodialysis were recruited: ten exercisers (age 42.4 +/- 12.6) and six controls (age 41.0 +/- 8.3). Both groups were initially tested for estimated VO(2max), heart rate, blood pressure, leg extension peak torque, anxiety and depression levels, as well as biochemical and haematological values. The exercisers then underwent cycling ergometer exercise sessions during dialysis, twice weekly, for a total of 12 sessions. Both groups were re-tested after this period. RESULTS: All test and exercise sessions were completed without complication. Compliance was high with only 1 exerciser failing to complete all 12 sessions. The exercisers showed a statistically significant increase (p < 0.05) in EDD workrates (44.3 to 52.1 watts) during the 12 sessions and a reduction in anxiety (p < 0.05). Statistical analysis showed no other significant changes in either group after the 6-week period. CONCLUSION: This pilot study has confirmed that aerobic EDD is feasible and well accepted by patients on hospital haemodialysis. EDD reduced anxiety scores and showed a trend for an improved level of aerobic fitness.

Urinary transferrin, high molecular weight proteinuria and the progression of renal disease.

AIMS: Proteinuria predicts rate of progression in a variety of nephropathies. There is considerable evidence that iron-transferrin is toxic to proximal tubular cells in vitro, and recent clinical work suggests that selectivity of proteinuria influences the outcome of renal disease. The aim of this study was to examine the relationship between the nature of proteinuria and progression of renal disease. METHODS: This was a prospective, cross-sectional study in 66 patients with primary glomerulonephritis, diabetic nephropathy and a variety of other renal diseases. Urinary transferrin was measured by sandwich ELISA and correlated with rate of change in estimated creatinine clearance (ECC). Urinary SDS-PAGE was undertaken to divide proteinuria into tertiles according to molecular weight and to quantify the protein in each tertile. The magnitude of each tertile was then correlated with rate of change in ECC over a median period of 20 months. RESULTS: Rate of change of renal function correlated with total proteinuria (r2 = 18%, p < 0.001) and albuminuria (r2 = 17%, p < 0.001), but not urinary transferrin (r2 = 0%, p = 0.235). On univariate analysis high molecular weight proteinuria (r2 = 21%, p < 0.001), intermediate molecular weight proteinuria (r2 = 15%, p = 0.001) and low molecular weight proteinuria (r2 = 10%, p = 0.005) correlated with rate of change in ECC as did total fasting cholesterol (r2 = 7%, p = 0.003). On multivariate analysis, however, the only independent predictors of rate of change in ECC were high molecular weight proteinuria (r2 = 19%, p < 0.001), and total fasting cholesterol (r2 = 5%, p = 0.035). CONCLUSIONS: We found no evidence to support the hypothesis that iron-transferrin is important in the development of human renal injury. High molecular weight proteinuria correlates more strongly with rate of progression of renal disease than intermediate molecular weight, low molecular weight or even total proteinuria. This suggests either, that one or more high molecular weightproteins are implicated in causing progressive renal impairment, or that loss of size selectivity at the glomerular basement membrane is associated with accelerated tubulointerstitial damage.

Serum creatinine can predict adequacy of peritoneal dialysis--preliminary report.

AIM: To determine the value of creatinine clearance, estimated using the Cockcroft and Gault formula, in assessing adequacy of peritoneal dialysis. METHODS: We undertook a retrospective analysis of creatinine clearance results derived from a conventional 24-hour collection in 35 stable outpatients on peritoneal dialysis and compared them with those calculated from the corresponding serum creatinine using the Cockcroft and Gault formula. RESULTS: There was a strong correlation between the 2 methods (r = 0.82, p < 0.0001), although the formula tended to over-estimate clearances. The formula had a positive predictive value of 88% and a negative predictive value of 86% for detecting inadequate dialysis. CONCLUSION: The creatinine clearance calculated using the Cockcroft and Gault formula can be used in patients on peritoneal dialysis to estimate adequacy of dialysis. We believe that this method, which is far less expensive and time-consuming, deserves further testing in a larger population in order to define more accurately its role in the management of PD patients.

Polymorphisms in angiotensin-converting-enzyme gene and progression of IgA nephropathy.

We have investigated the influence of the functional insertion (I) and deletion (D) polymorphism in intron 16 of the gene for angiotensin-converting enzyme (ACE) in a retrospective study of 100 patients with IgA nephropathy. There was no difference in genotype frequency compared with normal subjects. However, patients homozygous for the D allele tended to present at an earlier age (medians: DD, 33; ID, 34; II, 42 years) and to require renal replacement therapy at a younger age (medians 37, 42, and 48 years, respectively). The rate of progression was significantly worse in patients homozygous for the D allele. The DD genotype is associated with increased severity of disease in patients with IgA nephropathy.

Minimal change nephropathy in the west of Scotland: a review of sixty-four patients.

Sixty-four patients with a histological diagnosis of minimal change nephropathy have been followed for a median of 110 months. Patients transferred from paediatric units (11%) had a worse prognosis in that all became frequent relapsers. Patients who relapsed within three months or who went on to become frequent relapsers had a higher 24 hour urine protein excretion at presentation than patients who did not relapse. After fifteen months of remission relapse was rare; 97% of those who relapsed did so within 36 months. Patients who have been off steroids and proteinuria free for 36 months might therefore be considered cured.

Variations of glomerular properties and their effect on glomerular disease.

The possibility that inherited glomerular properties predispose individuals to certain glomerulopathies is an exciting new hypothesis. It opens new avenues to the investigation and treatment of patients which may be most easily applied in newly diagnosed diabetics and patients with multiple relapses of minimal change nephropathy. These treatments are unlikely to involve dangerous cytotoxic drugs which have been the fruit of years of investigation concentrated on the immune and inflammatory consequences of glomerular diseases. The differences between the two strains also cast doubt on the wisdom of extrapolating results obtained in the Munich Wistar rat to the rest of the animal kingdom.

Pharmacokinetics of clavulanic acid-potentiated ticarcillin in renal failure.

The serum kinetics of an intravenous bolus of a combination of ticarcillin (TIC) (3 g) and clavulanic acid (CLAV) (0.2 g) have been determined in a number of patients with different degrees of renal failure as characterized by creatinine clearance. The volume of distribution for both drugs was unaffected by renal failure. Indices of serum and renal drug clearance were related to the degree of renal failure. TIC was cleared more slowly than CLAV. Anephric patients may have a higher serum clearance of CLAV than patients categorized by creatinine clearance as having severe renal failure; this could be due to an increase in metabolic clearance. Haemodialysis effectively clears both drugs. "Rebound" serum concentrations were consistently observed for TIC, but were observed in only one patient for CLAV. Continuous ambulatory peritoneal dialysis results in significant recovery of both drugs. The dosing requirements for the combination of TIC and CLAV in patients with renal failure are considered.

Factors influencing mortality in malignant hypertension.

In a study designed primarily to assess mortality, 139 consecutive patients presenting with malignant hypertension (MHT) in Glasgow between 1968 and 1983 were matched individually for age, sex and initial blood pressure with 139 non-malignant hypertensives attending the Glasgow Blood Pressure Clinic. Fifty-four patients with MHT and 34 controls died before 1 April 1984. Multivariate analysis showed that initial serum creatinine and blood pressure achieved during treatment were significantly and independently related to outcome among the patients with MHT, but that age, smoking habit, presence of papilloedema, underlying diagnosis, initial blood pressure and year of presentation were not. Overall survival among patients with MHT was 63% at 5 years and 47% at 10 years. Although this was better than in earlier studies patients with MHT were still twice as likely to die as non-malignant controls. The excess mortality was confined largely to patients with underlying renal disease and/or renal failure at presentation. Moreover, renal failure contributed to four times more deaths among patients with MHT than controls. Thus, despite an improvement in survival compared with previous years, renal failure remains the most serious manifestation of patients with this disease.

Blood viscosity and haemostasis in the nephrotic syndrome.

Blood viscosity and its major determinants (haematocrit, plasma viscosity and fibrinogen) as well as several haemostatic variables were measured in 21 patients with the nephrotic syndrome, and 21 controls matched for age, sex, smoking habit and serum creatinine. Blood viscosity was significantly increased in the nephrotic group, measured at a low shear rate (mean increase 41%, p less than 0.01) and at a high shear rate (mean increase 25%, p less than 0.01). Haematocrit was not significantly increased, but plasma viscosity was significantly higher (p less than 0.01), associated with increased plasma macroglobulins especially fibrinogen, which was increased to double the plasma concentration of the control group (p less than 0.01). Nephrotic subjects also had increased plasma levels of alpha 2-macroglobulin, factor VIII activity, factor VIII antigen and beta-thromboglobulin; differences in antithrombin III, fibrin degradation products, plasminogen, and platelet count were not significant. We suggest that increased blood and plasma viscosity may play a role in the vascular complications of the nephrotic syndrome.

Clinical evaluation of a rosette inhibition test in renal allotransplantation.

The formation of spontaneous rosettes by peripheral blood or spleen mononuclear cells when incubated with sheep red blood cells has proved a useful way of assessing the potency of immunosuppressive drugs and antilymphocyte sera in vitro. A test employing the inhibition by antilymphocyte globulin (A.L.G.) of spontaneous rosette formation around peripheral blood mononuclear cells is described. This has been used to assess the degree of immunosuppression in patients with renal allografts and uraemic patients on regular haemodialysis.Twenty-three patients with renal allografts had 21 clinically diagnosed episodes of rejection. In none of these rejection episodes was the minimal inhibitory concentration (M.I.C.) of A.L.G. (that necessary to reduce the spontaneous rosette formation of peripheral cells by 75%) less than 1/50,000. Nineteen patients had no rejection episodes during 57 patient/months of continuous observation while the M.I.C. was at a greater dilution than 1/50,000. The test has therefore been of great value in suggesting when an individual is capable of rejecting his graft, and allows the dose of immunosuppressive drugs to be adjusted to a minimum in a controlled fashion. It has been of use in diagnosing rejection in the anuric patient, when the distinction between rejection, urinary tract obstruction, and infection is particularly difficult.Fifteen patients maintained on regular haemodialysis for more than a year had, as judged by this technique, less reactive lymphocytes than normal healthy controls. The degree of immunosuppression was not as great as in the patients on full immunosuppressive regimens.