Recent research in kidney transplantation. The Lilly lecture, 1969.
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Most tests of renal function assess glomerular function, tubular function, or renal plasma flow. Glomerular function should be determined initially by measuring clearance of endogenous creatinine. Tubular function is best determined clinically by measuring urine concentrating ability of the kidney. At present, no test for measuring renal plasma flow is both accurate and readily available.
Forty-four patients with definite or classical rheumatoid arthritis were entered in a 48-week open study, comparing the long-term effects of Timegadine and D-penicillamine. Twenty-three and 21 patients were respectively allocated to the Timegadine and D-penicillamine groups. Two patients of the former group were lost for follow-up, soon after the first baseline. Thus data were available only for 42 patients, 21 in each group of whom eleven completed the 48-week period in each group. Seven patients in the Timegadine group stopped because of ineffectiveness, 2 because of skin eruption and 1 because of acute interstitial pneumonitis. In the D-penicillamine group, 9 patients dropped out: 3 because of proteinuria, 2 because of stomatitis, 1 because of dizziness and 1 because of headache. Pain (visual analogue scale), number of swollen and painful joints improved significantly in both groups (p less than 0.05). The acute phase reactants alpha1-acid-glycoprotein and ESR and the thrombocyte count significantly decreased in the penicillamine group (p less than 0.05). The other clinical, hematological and immunological tests did not change; neither did the liver and kidney function tests. The clinical results suggest that Timegadine is as effective as D-penicillamine in the treatment of rheumatoid arthritis. D-penicillamine takes advantage over Timegadine by decreasing significantly the acute phase reactants. However, Timegadine has a low profile of side-effects.
Paracetamol poisoning is manifested by hepatotoxicity, but acute renal failure is very rare, especially when there is no fulminant hepatic damage with encephalopathy or severe haemodynamic alterations. We present here the case of a 22-year-old woman who presented with acute renal failure after the ingestion of 11.5 g of acetaminophen. The clinical course and laboratory data were consistent with tubular necrosis. The patient required hemodialysis, but finally renal function returned to normal. The acetaminophen pharmacology and the differential diagnosis of acute azotemia in paracetamol overdosage are reviewed.
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OBJECTIVES: To determine whether data on proteinuria are useful for refining estimates of risk based on kidney function alone, and whether the results of kidney function tests can be a useful adjunct to data on proteinuria. DESIGN: Analysis of data from a randomised trial. Impaired kidney function was defined as low glomerular filtration rate (< 60 ml/min/1.73 m2) and proteinuria (> or = 1+ protein) on dipstick urinalysis. SETTING: Study of cholesterol and recurrent events: a randomised trial of pravastatin 40 mg daily versus placebo. PARTICIPANTS: 4098 men and women with previous myocardial infarction. MAIN OUTCOME MEASURES: All cause mortality and cardiovascular events. RESULTS: 371 participants died in nearly 60 months of follow-up. Compared with participants without proteinuria or impaired kidney function, patients with both characteristics were at high risk (hazard ratio 2.39, 95% confidence interval 1.72 to 3.30), and those with only proteinuria or only impaired kidney function were at intermediate risk (1.69, 1.32 to 2.16; 1.41, 1.12 to 1.79, respectively) of dying from any cause. The results were similar for cardiovascular outcomes, including new cases of heart failure, stroke, and coronary death or non-fatal myocardial infarction. A graded increase in the risk of all cause mortality was seen for severity of renal impairment and degree of proteinuria by dipstick. CONCLUSIONS: The presence or absence of proteinuria on dipstick urinalysis may be used to refine estimates of risk based on kidney function alone.
Renal functional reserve capacity was evaluated in healthy controls, kidney transplant recipients and patients with impaired liver function by simultaneous measurements of periodic clearances of inulin, PAH and creatinine every 30 minutes before, during and after infusion of an amino acid (AA) solution. During AA infusion glomerular filtration rate rose in 10 healthy controls to about 35% above basal values (inulin clearance from 107 +/- 6 to 144 +/- 7 ml/min, p less than or equal to 0.0005), renal plasma flow increased by 27% (PAH clearance from 530 +/- 25 to 675 +/- 40 ml/min, p less than or equal to 0.002). 8 renal transplant recipients with good and stable renal function (creatinine clearance above 65 ml/min) showed no rise in GFR and RPF, as did 10 patients with severe impairment of liver function and normal basal kidney function (creatinine clearance above 100 ml/min). The lack of renal functional reserve in kidney transplant recipients might indicate a hyperfiltration of the transplanted kidney. This could affect the longtime prognosis of these patients. The liver seems to play a role in the mediation of the amino acid-induced rise of GFR, supporting the hypothesis of a putative liver hormone regulating GFR after protein ingestion or AA infusion.
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UNLABELLED: Seven patients with histologically proven IgA nephropathy and modest impairment of renal function, and 2 patients with IgA nephropathy and nephrotic syndrome were investigated, compared to a control group of 9 healthy individuals, to study the effects of amino acids on glomerular and tubular function, and to evaluate renal functional reserve in IgA nephropathy with different clinical course. Inulin and PAH clearances were used to evaluate glomerular filtration rate (GFR) and effective renal plasma flow (ERPF); proximal and distal tubular fluid delivery and reabsorption were measured by lithium clearance, before and after submission of a standardized amino acid solution. GFR and ERPF increased significantly during amino acid load in healthy individuals and patients without nephrotic syndrome, while filtration fraction (GFR/ERPF) remained constant. Lithium clearance (CLi) and fractional lithium excretion (CLi/GFR) rose significantly in both groups, whereas the reabsorbed volume of fluid in the proximal tubule did not change. In the distal tubule, fractional volume excretion decreased significantly during amino acid load whereas the reabsorbed volume significantly increased. Baseline values of the two groups did not differ significantly. Two patients with nephrotic course of IgA nephropathy showed a distinct decrease in glomerular and tubular function, and a loss of renal functional reserve after amino acid load. CONCLUSIONS: Despite distinct alterations in renal biopsy, IgA nephropathy without nephrotic course presents with a still adequately preserved kidney function and renal functional reserve. A single determination of renal function with noninvasive functional tests does not give valid prognostic information concerning glomerular and tubular function. Therefore, a repeated measurement of renal function at defined intervals might reveal clinical progression of renal disease. The results of the lithium clearance might indicate an increase in tubular function after amino acid load, indicating a tubular adaptation in state of hyperfiltration.
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