Paul Jungers

Octogenarians Reaching End-Stage Renal Disease: Cohort Study of Decision-Making and Clinical Outcomes

The fate of octogenarians reaching end-stage renal disease (ESRD) is poorly defined, and implicit dialysis rationing may be practiced in this age group. The main objectives of this study were to analyze the characteristics of pre-ESRD octogenarians offered dialysis or not and to identify factors influencing mortality while on dialysis, to improve prognosis assessment and decision-making. In this single-center cohort, 146 consecutive pre-ESRD octogenarians were referred to a nephrology unit over a 12-yr period (1989 to 2000). Main outcome measures were baseline characteristics of patients offered dialysis and conservative therapy and overall and 1-yr survival according to effective treatment. A therapeutic decision was made for 144 patients. Octogenarians who were not proposed dialysis (n = 37) differed from those who were proposed dialysis (n = 107) mainly in terms of social isolation (43.3% versus 14.7%; P = 0.03), late nephrologic referral (51.4% versus 28.9%; P = 0.01), Karnofsky score (55 +/- 18 versus 63 +/- 20; P = 0.03), and diabetic status (22.2% versus 6.5%, P = 0.008). Six patients refused the dialysis proposal. During the 12-yr observation period, 99 patients died (68.7%). Median survival was 28.9 mo (95% CI, 24 to 38) in patients undergoing dialysis, compared with 8.9 mo (95% CI, 4 to 10) in patients treated conservatively (P < 0.0001). In multivariable piecewise Cox analysis, independent predictors of death within 1 yr on dialysis were poor nutritional status, late referral, and functional dependence. Included in a survivor function, these covariates predict groups with low and high 1-yr mortality risk. Beyond 1 yr on dialysis, the only independent predictor of death was the presence of peripheral vascular disease. It is concluded that beside a patients individual refusal, late referral, social isolation, low functional capacity, and diabetes may have oriented medical decision toward withholding dialysis in a significant proportion of pre-ESRD octogenarians. Although most patients on dialysis experienced a substantial prolongation of life, identification of mortality predictors in this age group should improve the process of decision-making regarding the expected benefit of renal replacement therapy.

Type 2 Diabetes Increases the Risk for Uric Acid Stones

An increased prevalence of nephrolithiasis has been reported in patients with diabetes. Because insulin resistance, characteristic of the metabolic syndrome and type 2 diabetes, results in lower urine pH through impaired kidney ammoniagenesis and because a low urine pH is the main factor of uric acid (UA) stone formation, it was hypothesized that type 2 diabetes should favor the formation of UA stones. Therefore, the distribution of the main stone components was analyzed in a series of 2464 calculi from 272 (11%) patients with type 2 diabetes and 2192 without type 2 diabetes. The proportion of UA stones was 35.7% in patients with type 2 diabetes and 11.3% in patients without type 2 diabetes (P < 0.0001). Reciprocally, the proportion of patients with type 2 diabetes was significantly higher among UA than among calcium stone formers (27.8 versus 6.9%; P < 0.0001). Stepwise regression analysis identified type 2 diabetes as the strongest factor that was independently associated with the risk for UA stones (odds ratio 6.9; 95% confidence interval 5.5 to 8.8). The proper influence of type 2 diabetes was the most apparent in women and in patients in the lowest age and body mass index classes. In conclusion, in view of the strong association between type 2 diabetes and UA stone formation, it is proposed that UA nephrolithiasis may be added to the conditions that potentially are associated with insulin resistance. Accordingly, it is suggested that patients with UA stones, especially if overweight, should be screened for the presence of type 2 diabetes or components of the metabolic syndrome.

RANDOMISED PLACEBO-CONTROLLED TRIAL OF HEPATITIS B SURFACE ANTIGEN VACCINE IN FRENCH HAEMODIALYSIS UNITS: II, HAEMODIALYSIS PATIENTS

A vaccine against hepatitis B surface antigen (Institut Pasteur Production) was assessed in 138 haemodialysis patients in a placebo-controlled randomised double-blind trial. In an interim analysis, hepatitis B infections were observed in 21% of the vaccine group and 45% of the placebo group (p less than 0.02). 2 of the infections in the vaccine group and 12 of the infections in the placebo group occurred after the third injection. 60% of the vaccine recipients had an immune response. 4 months after the first injection the mean titre of anti-HBs was 120 mlU/ml.

RANDOMISED PLACEBO-CONTROLLED TRIAL OF HEPATITIS B SURFACE ANTIGEN VACCINE IN FRENCH HAEMODIALYSIS UNITS: I, MEDICAL STAFF

A vaccine against hepatitis B surface antigen (Institut Pasteur Production) was assessed in staff members from forty-eight French haemodialysis units where the risk of hepatitis B was high. Of 318 subjects who completed the protocol, 164 received three monthly injections of vaccine and 154 received corresponding injections of placebo. Hepatitis B infection was observed in 3.6% of the vaccine group and 12.3% of the placebo group (p less than 0.005). The 6 infections in the vaccine group all arose within 63 days from the first injections, whereas the 19 in the placebo group arose throughout the 12 months of follow-up. The rate of side-effects after injection did not differ in the two groups. 94% of the vaccine recipients had an immune response ( greater than 10 mIU/ml in at least 5 successive specimens). 4 months after the first injection the mean + or - 2 SE peak level of anti-HBs was 2433 + or - 1077 mIU/ml.

Changes in stone composition according to age and gender of patients: a multivariate epidemiological approach

Urinary stone incidence and composition have changed markedly over the past half-century in industrialized countries, in parallel with profound changes in living standards and dietary habits, with a dramatic increase in the incidence of calcium oxalate stones. However, studies evaluating the influence of age and gender on the distribution of the various types of urinary calculi are scarce. We report the results of a study based on 27,980 calculi (from 19,442 males and 8,538 females) analyzed by infrared spectroscopy between 1976 and 2001. The relationships between age and sex and stone composition were investigated using a multivariate approach, based on correspondence factor analysis (CFA). We found a male predominance for calcium oxalate and uric acid, a female preponderance for calcium phosphate and struvite stones, and an increasing prevalence of uric acid stones with age in both genders. CFA was able to reconstruct in blind the age curve from stone composition. The first two axes of the multidimensional classification, which correspond to age, included 86.9% of the total variance, indicating that age was the main factor involved in stone type. Superimposition of age classes and stone components showed a strong relationship between age and whewellite, weddellite, brushite, carbapatite, octacalcium phosphate and uric acid, while other substances (whitlockite, amorphous carbonated calcium phosphate, struvite, proteins, mucopolysaccharides, triglycerides or ammonium urate) appeared weakly related to age. In addition, CFA suggests the role of common lithogenic factors between weddellite, carbapatite and brushite, which clustered in the same area, whereas the various crystalline forms of phosphate stones segregated into two different clusters, suggesting distinct pathogenic factors. In conclusion, this study provides a picture of the present epidemiology of urinary stones in France. CFA helped to confirm: (1) an etiopathogenic distinction between weddellite and whewellite, (2) etiopathogenic associations between chemical compounds, which were only suspected on a clinical basis, and (3) suggested yet unrecognized associations, especially with respect to the heterogeneous group of phosphate stones.

Drug-induced renal calculi: Epidemiology, prevention and management

Drug-induced calculi represent 1–2% of all renal calculi. The drugs reported to produce calculi formation may be divided into two groups.The first one includes poorly soluble drugs with high urine excretion that favours crystallisation in the urine. Among poorly soluble molecules, triamterene was the leading cause of drug-containing urinary calculi in the 1970s, and it is still currently responsible for a significant number of calculi. In the last decade, drugs used for the treatment of HIV-infected patients, namely indinavir and sulfadiazine, have become the most frequent cause of drug-containing urinary calculi. Besides these drugs, about twenty other molecules may induce nephrolithiasis in patients receiving long-term treatment or high doses. Calculi analysis by physical methods, including infrared spectroscopy or x-ray diffraction, is needed to demonstrate the presence of the drug or its metabolites within the calculi.The second group includes drugs that provoke urinary calculi as a consequence of their metabolic effects. Here, diagnosis relies on careful clinical inquiry because physical methods are ineffective to differentiate between urinary calculi induced by the metabolic effects of a drug and common metabolic calculi. The incidence of such calculi, especially those resulting from calcium/vitamin D supplementation, is probably underestimated.Although drug-induced urinary calculi most often complicate high-dose, long-duration drug treatments, there also exist specific patient risk factors in relation to urine pH, urine output and other parameters, which provide a basis for preventive or curative treatment of calculi.Better awareness of the possible occurrence of lithogenic complications, preventive measures based on drug solubility characteristics and close surveillance of patients on long-term treatment with drugs with lithogenic potential, especially those with a history of urolithiasis, should reduce the incidence of drug-induced nephrolithiasis.

Clinical Value of Crystalluria and Quantitative Morphoconstitutional Analysis of Urinary Calculi

Morphoconstitutional analysis of urinary calculi, i.e. morphologic examination combined with Fourier transform infrared spectroscopy (FTIR), is of decisive interest for the diagnosis of rare but severe inherited or acquired stone diseases such as cystine, 2,8-dihydroxyadenine, xanthine, struvite, ammonium urate or drug-containing calculi as well as primary hyperoxalurias. In the absence of early diagnosis and proper management, these diseases may lead to progressive loss of renal function. Among common forms of calcium oxalate (CaOx) stones, predominant CaOx monohydrate (whewellite) is mainly associated with hyperoxaluric conditions whereas predominant CaOx dihydrate (weddellite) is mainly associated with hypercalciuria, and this distinction is of interest to orient metabolic evaluation and preventive measures. Crystalluria examination, also based on morphology and FTIR, is a valuable diagnostic method when no stone is available for analysis. Presence of specific crystals (cystine, 2,8-dihydroxyadenine, struvite, ammonium urate) is diagnostic by itself. In all types of nephrolithiasis, serial crystalluria determination appears as a simple, cheap and reliable method to evaluate the risk of stone formation and assess the effectiveness of preventive measures. Determination of urinary crystal volume was in our experience a useful tool in the management of patients with cystinuria or primary hyperoxaluria in the post-transplantation period. In conclusion, both accurate morphologic and FTIR analysis of stones and serial crystalluria determination should be more largely used, in view of their value in the diagnosis and management of renal stone formers.

Influence of pregnancy on the course of primary chronic glomerulonephritis

According to some nephrologists, pregnancy has damaging effects on renal function in primary glomerulonephritis, but the evidence is conflicting. We evaluated the effect of pregnancy on the occurrence of end-stage renal failure (ESRF) in 360 patients with various histological forms of primary glomerulonephritis but with normal renal function (serum creatinine < or = 0.11 mmol/L) at presentation. In actuarial analyses, overall ESRF-free survival did not significantly differ between women who became pregnant after clinical onset of renal disease (n = 171) and those who did not conceive (n = 189). Furthermore, in a case-control study pregnancy did not emerge as a risk factor for progression to ESRF (odds ratio 1.15 [95% CI 0.61-2.18]), whereas the type of glomerulonephritis and hypertension were major determinants. We conclude that pregnancy does not affect the course of renal disease in patients who have normal renal function at conception.

Osmotic Nephrosis Induced by Water-Soluble Triiodinated Contrast Media in Man

Renal biopsies were performed in 211 patients which 10 days of excretory urography or renal arteriogrpahy in which diatrizoate, iothalamate or ioxithalamate had been used. In 47 renal specimens, osmotic nephrosis of the proximal tubular cells was found. Previous renal function had been normal in 10 patients, moderately impaired in 19, and severely impaired in 18. Tubular atrophy and/or necrosis was associated with histological features in 29 of 47 patients. Diffuse osmotic nephrosis was more often found in patients biopsied soon after roentgenography and also with severe renal insufficiency, but was not necessarily associated with declining renal function. The mechanism(s) by which contrast media may induce osmotic nephrosis remains unclear.

Heavy elements in urinary stones

The presence and role of heavy metals in urinary stones is debated. We investigated the distribution of trace heavy metals in 78 calculi of well-defined composition by means of microfluorescence X analysis using synchrotron radiation. Seven elements were identified, the most abundant being Zn and Sr which together accounted for 91% of the heavy metal content of stones. The other heavy metals were Fe, Cu, Rb, Pb and Se. Zn and Sr were virtually confined to calcium-containing stones, whereas only trace amounts were found in uric acid or cystine stones. Among calcium stones, Zn and Sr were more abundant in calcium phosphate than in calcium oxalate stones and, in the latter, in weddellite than in whewellite stones. Fe, Cu and Rb were much less abundant and also found mainly in calcium stones. Pb was significantly less abundant than in previous studies, thus suggesting a rarefaction of Pb in the environment, and appreciable amounts of Se were found only in cystine stones. In conclusion, the preponderance of Zn and Sr, both bivalent ions, in calcium-containing stones suggests a substitution process of calcium by metal ions with similar charge and radius rather than a contribution of the metals to stone formation. Further studies are needed to examine the relationships between urine concentration in calcium or other solutes and the amount of Zn and Sr in calcium stones.