L-arginine supplementation in young renal allograft recipients with chronic transplant dysfunction.

AIMS: L-arginine (LA), the precursor of nitric oxide (NO), was suggested to be beneficial in many forms of renal disease: hypertension, ureteral obstructive nephropathy and cyclosporin A (CsA) nephrotoxicity. METHODS: Thus, we investigated the effects of LA supplementation on renal function, proteinuria and blood pressure (BP) in young renal allograft recipients with chronic renal transplant dysfunction treated with CsA. Eleven CsA-treated renal allograft recipients with chronic transplant dysfunction, aged 11-22 years, were randomly assigned to a 6-week treatment period with placebo (P), followed by 2 subsequent 6-week periods with LA supplementation (0.1 g/kg body weight/day) or a 6-week treatment period with LA, followed by 2 subsequent 6-week periods with P. At the end of each treatment period 24-hour BP recordings were made, and GFR (Inutest), RPF (PAH clearance) and the urinary excretion of protein, albumin, nitrate, cGMP and urea were evaluated. RESULTS: In comparison to placebo, LA treatment did not significantly change GFR, RPF, proteinuria and albuminuria, mean systolic or diastolic BP. The urinary excretion of urea and NO3 increased after LA supplementation (uUrea: LA 26.3 +/- 4.6 compared to P 23.5 +/- 4.7 g/day/1.73 m3, p < 0.05, uNO3: LA 514 +/- 152 compared to P 95 +/- 41 mM/day/1.73 m3, p < 0.05), whereas urinary excretion of cGMP remained unchanged. CONCLUSION: LA supplementation did not improve renal function and did not decrease proteinuria in CsA-treated renal allograft recipients with chronic transplant dysfunction possibly because of inhibition of NO-cGMP forming mechanism.

No difference in intestinal strontium absorption after oral or IV calcitriol in children with secondary hyperparathyroidism. The European Study Group on Vitamin D in Children with Renal Failure.

BACKGROUND: Oral and intravenous calcitriol bolus therapy are both recommended for the treatment of secondary hyperparathyroidism, but it has been claimed that the latter is less likely to induce absorptive hypercalcemia. The present study was undertaken to verify whether intravenous calcitriol actually stimulates intestinal calcium absorption less than oral calcitriol and whether it is superior in suppressing parathyroid hormone (PTH) secretion. METHODS: Twenty children (16 males, age range of 5.1 to 16.9 years, mean creatinine clearance 21.9 +/- 11.5 mL/min/1.73 m2, range of 7.4 to 52.7) with chronic renal failure (CRF) and secondary hyperparathyroidism [median intact PTH (iPTH), 327 pg/mL; range 143 to 1323] received two single calcitriol boli (1.5 mg/m2 body surface area) orally and intravenously using a randomized crossover design. iPTH and 1,25(OH)2D3 levels were measured over 72 hours, and intestinal calcium absorption was measured 24 hours after the calcitriol bolus using stable strontium (Sr) as a surrogate marker. Baseline control values for Sr absorption were obtained in a separate group of children with CRF of similar severity. RESULTS: The peak serum level of 1,25(OH)2D3 and area under the curve baseline to 72 hours (AUC0-72h) were significantly higher after intravenous (IV) calcitriol (AUC0-72h oral, 1399 +/- 979 pg/mL. hour vs. IV 2793 +/- 1102 pg/mL. hour, P < 0.01), but the mean intestinal Sr absorption was not different [SrAUC0-240min during the 4 hours after Sr administration 2867 +/- 1101 FAD% (fraction of the absorbed dose) vs. 3117 +/- 1581 FAD% with oral and IV calcitriol, respectively]. The calcitriol-stimulated Sr absorption was more then 30% higher compared with control values (2165 +/- 176 FAD%). A significant decrease in plasma iPTH was noted 12 hours after the administration of the calcitriol bolus, which was maintained for up to 72 hours without any differences regarding the two routes of administration. CONCLUSIONS: These results demonstrate that under acute conditions, intravenous and oral calcitriol boli equally stimulate calcium absorption and had a similar efficacy in suppressing PTH secretion.

Calcitriol pulse therapy is not more effective than daily calcitriol therapy in controlling secondary hyperparathyroidism in children with chronic renal failure. European Study Group on Vitamin D in Children with Renal Failure.

Calcitriol oral pulse therapy has been suggested as the treatment of choice for secondary hyperparathyroidism, but its efficacy and safety are still under discussion. The present randomized multicenter study compares the effect of an 8-week course of daily versus intermittent (twice weekly) calcitriol therapy on parathyroid hormone (PTH) suppression in 59 children (mean age 8.4+/-4.7 years) with chronic renal insufficiency (mean Ccr 22.4+/-11.6 ml/min per 1.73 m2) and secondary hyperparathyroidism. After a 3-week washout period, the patients were randomly assigned to treatment with daily oral calcitriol (10 ng/kg per day) or intermittent oral calcitriol (35 ng/kg given twice a week). The calcitriol dose was not changed throughout the study period of 8 weeks. At start of the study, the median intact PTH (iPTH) level was 485 pg/ml (range 83-2032) in the daily group (n=29) and 315 pg/ml (range 93-1638) in the intermittent group (n=30). After 8 weeks, the respective median iPTH concentrations were 232 pg/ml (range 63-1614) and 218 pg/ml (range 2-1785) (ns). The mean iPTH decrease from baseline was 19.2+/-57.8% and 13.7+/-46.7% respectively (not significant). Calcitriol reduced the iPTH concentration in 23/29 patients in the daily group and in 21/30 in the intermittent group. One episode of hypercalcemia (>11.5 mg/dl) was observed in both groups and a single episode of hyperphosphatemia (>7.5 mg/dl) was observed in the daily group. It is concluded that oral calcitriol pulse therapy does not control secondary hyperparathyroidism more effectively than the daily administration of calcitriol in children with chronic renal failure prior to dialysis.

No difference in intestinal strontium absorption after an oral or an intravenous 1,25(OH)2D3 bolus in normal subjects. For the European Study Group on Vitamin D in children with renal failure.

It has been suggested that 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) stimulates intestinal calcium absorption less via the intravenous (iv) than the oral route, because the first avoids direct contact of the drug with the enterocytes. However, no study has addressed the issue directly. This investigation was designed to measure the effect of a single oral or iv dose of 1,25(OH)2D3 on calcium absorption, using stable strontium (Sr) as a surrogate for calcium, and measuring the Sr fractional absorbed dose (FAD%) over 240 minutes after Sr administration. In 10 healthy volunteers, five tests were performed in a cross-over design, with a wash-out period between two consecutive tests: Sr absorption without 1,25(OH)2D3 (test A); Sr absorption immediately after either oral (test B) or iv (test C) 1,25(OH)2D3 (1.5 microg/m2 of body surface area [BSA]); Sr absorption (24 hr after either oral (test D) or iv (test E) 1, 25(OH)2D3 (1.5 microg/m2 BSA). The concurrent administration of 1, 25(OH)2D3 and Sr (tests B and C) did not significantly change the area under the Sr FAD%-time curve with respect to test A (test A: 4090 +/- 345; test B: 4510 +/- 345; test C: 4210 +/- 345), whereas Sr absorption was significantly increased (p < 0.001) when Sr was given 24 hr after either oral or iv 1,25(OH)2D3 (test D: 5710 +/- 345; test E: 5510 +/- 345). It was concluded that 1,25(OH)2D3 is likely to influence calcium absorption significantly only via its genomic effect, independent of its administration route.

Renal and metabolic effects of L-arginine infusion in kidney transplant recipients.

AIM AND METHODS: In order to investigate the role of kidney damage on renal response to L-arginine (L-Arg) infusion in transplant patients receiving cyclosporine A (CsA) treatment, we assessed systemic and glomerular hemodynamic variables, the fraction excretion of urinary sodium, albumin, cyclic GMP (as an index of nitric oxide (NO) production from L-Arg) and urea excretion (as an index of ureagenesis), and glucoregulatory hormone levels in five normal volunteers and 21 renal allograft recipients (aged 10-20 years) treated with CsA, 10 with normal renal function and 11 with chronic renal insufficiency. RESULTS: In the normal subjects, L-Arg infusion (290 mg/min/1.73 m2 for 1 h) significantly reduced mean arterial pressure (MAP) (76+/-7 to 70+/-5 mmHg) and renal vascular resistance (RVR), and increased GFR (103+/-9 to 122+/-7 min/1.73 m2), RPF, urinary cyclic GMP excretion (0.40+/-0.1 to 0.60+/-0.1 nmol/100 ml glomerular filtrate (GF)), and sodium and albumin excretion. Neither the patients with chronic graft dysfunction nor those with a normal graft responded to L-Arg infusion: RVR remained high, and MAP, GFR, RPF, fractional excretion of sodium and urinary excretion of albumin and cyclic GMP were unchanged in both groups of patients. Glucagon, insulin and urinary urea excretion rose significantly in controls and both patient groups. CONCLUSION: The hemodynamic effects of L-Arg infusion were inhibited in the patients, regardless of their degree of renal function, possibly because L-Arg-NO production was blunted.

Hypotonic saline infusion alters the renal response to amino acids in men.

We investigated the effects of hypotonic saline-induced modifications of extracellular volume and sodium handling on the renal and metabolic response to amino acids (AA). Renal hemodynamics (Inutest, p-aminohippurate clearance), plasma AA, and glucagon levels, as well as urea and sodium excretion, were studied in seven adult volunteers infused for 2 h, on six separate occasions, according to the following protocols: 1) high-AA solution (300 mg. min-1. 1.73 m-2); 2) low-AA solution (150 mg. min-1. 1.73 m-2); 3) low AA + 2,000 ml/1.73 m2 of 0.23% saline solution; 4) high AA + 0. 23% saline; 5) high AA + 0.45% saline; and 6) 0.45% saline alone. The glomerular filtration rate (GFR) rise induced by the high-AA solution was similar to that induced by the low-AA solution (DeltaGFR = +24 +/- 6 and +20.2 +/- 7 ml. min-1. 1.73 m-2, respectively), whereas the plasma AA and glucagon levels and urea excretion rate increases were related to AA dose. The addition of 0. 23% saline to the low-AA solution and of 0.45% saline to the high-AA solution blunted the renal hemodynamic response (DeltaGFR = +6.6 +/- 10.1 and +11.4 +/- 8.3 ml. min-1. 1.73 m-2, respectively) without modifying the pattern of plasma AA and glucagon levels and urea excretion observed with the AA infusion alone. Urinary sodium excretion increased from baseline with each protocol and rose even further when saline was added to AA. A negative correlation (r = -0. 38, P < 0.05) was found between the changes from basal values in GFR and those in sodium excretion rate with high-AA infusion at different levels of sodium concentration. These data suggest that AA-induced hyperfiltration might be blunted by hypotonic saline infusion, possibly through an acute modification of renal sodium handling and extracellular volume.

Metabolic factors in the renal response to amino acid infusion.

In order to investigate the renal effects of amino acids (AA) with different metabolic fate, we compared the changes in glomerular and tubular function, nitrogen metabolism and glucoregulatory hormones in 7 volunteers during two infusions, one of a complete solution of amino acids (MIX-AA), which included five AA electively metabolized at the splanchnic level, and the other of a solution containing only essential AA (EAA), which escape splanchnic metabolism. MIX-AA increased GFR and RPF (from 104 +/- 6 to 122 +/- 13 and from 488 +/- 46 to 572 +/- 34 ml/min/1.73 m2), stimulated splanchnic metabolism as demonstrated by rises in urinary urea excretion (from 20.7 +/- 2 to 30.6 +/- 7.5 mg/min/1.73 m2) and the plasma glucagon/insulin ratio (from 21.4 +/- 13 to 26.7 +/- 15), and caused increases in fractional excretion of AA, FeNa and free-water clearance. During MIX-AA infusion significant correlations were observed between the individual values of GFR and the urea excretion rate (r = 0.66), and between GFR modifications (DeltaGFR) and the plasma glucagon/plasma insulin ratio (r = 0.40). No change in renal function, urea excretion and the glucagon/insulin ratio was observed with EAA. An intermediate splanchnic step (increased plasma glucagon/insulin ratio and ureagenesis) seems necessary in the pathway leading to the nonessential AA-induced rise in GFR; this might stimulate an ultimate intrarenal pathway (possibly involving the diluting segment) via a still undefined mechanism.

Catch-up growth in children with chronic renal failure treated with long-term enteral nutrition.

Growth retardation commonly complicates chronic renal failure in children. Although the etiology of this growth impairment is multifactorial, inadequate nutrition is considered an important cause in infants and young children. An "aggressive" nutritional approach has been repeatedly suggested in children with early onset chronic renal failure and poor feeding habits, but the possibility of inducing catch-up growth by energy supplementation is still controversial. The nutritional effects of a long-term, home-based enteral feeding program were studied in two infants and three children with moderate to severe chronic renal failure and impaired growth associated with persistent anorexia. In all patients, renal failure had developed during the first year of life due to congenital diseases. Enteral feeding was performed at home, during the night, through a silicone rubber nasogastric tube. The treatment lasted for 1 year. The energy intake ranged between 101% and 116% of the recommended dietary allowance (RDA), and the protein intake between 96% and 113% of the RDA in all patients but one, in whom proteins were restricted to 75% of the RDA. All children showed a substantial improvement in deviation score for both weight (mean increase +1.76), height (mean increase +1.52) and in the general metabolic condition, irrespective of age, severity of osteodystrophy, or degree of renal failure. The treatment was well tolerated and, apart from a few episodes of vomiting, no complications arose during the treatment. Tube feeding may be an effective therapeutic option for overcoming malnutrition when chronic renal failure is associated with persistent anorexia. In infants and young children, growth retardation can be opposed and catch-up growth obtained.

Intramuscular calcitriol for uraemic children with severe hyperparathyroidism and hypercalcaemia.

The effect of intramuscular calcitriol was evaluated in five children (aged 1-16 years) with severe chronic renal failure and hyperparathyroidism [range of intact parathyroid hormone (PTH) 400-1,200 pg/ml]. All five children had been on oral calcitriol or 1 alpha-hydroxyvitamin D3 treatment (5-20 ng/kg per day), but an adequate, efficacious dosage could not be achieved since any attempt of increasing the dosage resulted in severe hypercalcaemia (> 2.9 mmol/l). Intramuscular calcitriol was given three times weekly for 5 months at an initial dosage of 65-70 ng/kg to all but one patient who received 100 ng/kg. In the first three patients, treatment resulted in an 86%-98% fall in serum PTH compared with baseline levels and serum calcium never exceeded 2.65 mmol/l, except for one episode of hypercalcaemia in one patient. In the last two patients, serum calcium rose above normal limits, thus calcitriol had to be discontinued several times and then restarted at a lower dosage (40 ng/kg); PTH fell by 61% and 73%, respectively, compared with basal values. All patients had very low pre-treatment levels of serum 1,25-dihydroxyvitamin D3 (5-15 pg/ml) which were normalized (35-56 pg/ml) by the intramuscular calcitriol-treatment. Serum phosphorus and magnesium did not vary in any of the five patients. No side effects were observed at the injection site. Intramuscular calcitriol seems a useful therapeutic option for patients with severe hyperparathyroidism associated with a high serum calcium level when treated with conventional oral calcitriol.

Increased sodium requirement following early postnatal surgical correction of congenital uropathies in infants.

Serum electrolyte equilibrium and plasma aldosterone concentrations were monitored in 19 infants who had severe obstructive uropathy or grade 5 vesico-ureteral reflux and were undergoing surgical correction in the first 2 months of life. Before surgery high plasma aldosterone levels were observed in 8 patients, but serum sodium and potassium concentrations were normal. Plasma concentrations of aldosterone were elevated in all patients during the week following surgery and 7 patients developed severe hyponatraemia, hyperkalaemia and weight loss despite very high plasma aldosterone concentrations. As a consequence 5 infants were infused with sodium chloride (4 mEq/kg per day) before and for 36 h after surgery; this prevented metabolic imbalance. We conclude that infants undergoing surgical correction of uropathies may require a high sodium intake to maintain electrolyte balance and adequate growth.

Growth in young children with chronic renal failure.

Statural growth and its relation to growth potential, renal function, blood urea nitrogen (BUN), mineral metabolism hormones and dietary intake were studied in 17 prepubertal children (aged 1.6-9.3 years) on conservative treatment for chronic renal failure due to tubulo-interstitial nephropathy. Statural growth (height SDS) was related to the degree of renal failure, was more retarded than ossification, and was independent of the chronological age of the patients. We observed that the lower the glomerular filtration rate (GFR), the lower was the growth potential (increased bone age/statural age ratio). Growth velocity may be normal regardless of statural and bone maturation delay and the degree of renal insufficiency. Impaired growth rate correlated with parathyroid hormone levels, caloric intake and increased blood urea nitrogen during the year of observation. These data show that comprehensive monitoring and suitable treatment must be performed in order to prevent growth retardation at any GFR level.

Plasma infusion for hemolytic-uremic syndrome in children: results of a multicenter controlled trial.

The results of a controlled trial to ascertain the usefulness of plasma infusion for the treatment of hemolytic-uremic syndrome (HUS) are reported. Criteria for admission were (1) observation within 8 days from first symptoms, (2) dialysis treatment required, and (3) no special treatments and no more than 25 ml blood/kg previously received. Children were subdivided according to age (less than or more than 3 years) and then randomly assigned to treatment with plasma or symptomatic therapy. Thirty-two children ranging in age from 4 months to 6 years entered this study; 17 received plasma (P+ group) and 15 only symptomatic therapy (P- group). The mean follow-up period was 16 months in both groups. Surgical renal biopsy was performed 29 to 49 days after onset in 11 P+ and 11 P- children, and 33 histologic findings were semiquantitatively evaluated. No death occurred in either group. No differences were found in blood pressure, proteinuria, or hematuria at the end of the follow-up period; in no case were severe arteriolar lesions found. There were no significant differences for the scores of the individual histologic measurements; on electron microscopy, no vascular changes were observed in seven children of the P+ group, whereas in five of seven of the P- group, thickening of the lamina rara interna and arteriolar damage were present. The ability of plasma to stimulate prostacyclin (PGI2) production, measured as its stable derivative 6-keto-PGF1 alpha, was within the normal range for all patients. In our patients with predominant glomerular involvement who were treated in a very early phase of HUS, infusions of plasma did not significantly influence the short- and medium-term clinical outcome and were not effective in severe HUS when given later in the course of the disease. A longer follow-up is needed to ascertain whether the presence of endothelial damage, demonstrated by electron microscopy in children who were not given plasma, is of clinical relevance.

Lack of glomerular hemodynamic stimulation after infusion of branched-chain amino acids.

Renal hemodynamics (Inutest. CPAH) were studied in five adult volunteers infused on separate occasions with branched-chain amino acids (BCAA), a mixture of nonessential and essential amino acids of the same volume, osmolality and nitrogen content, and 0.9% saline solution. BCAA infusion caused moderate renal vasoconstriction, a slight increase of GFR and a progressive rise of the filtration fraction (FF), whereas the amino acids mixture induced a significantly higher increase of GFR and a state of renal vasodilatation without altering the FF. The volume expansion with 0.9% saline did not cause any notable hemodynamic modification except for reduced FF. This study demonstrates that whereas a state of hyperfiltration and hyperemia is specifically induced by an amino acid mixture independently of volume expansion and osmolar load, the administration of BCAA provides nitrogen without renal hemodynamic stimulation.

Proximal tubular function and hyperfiltration during amino acid infusion in man.

The relations between renal hemodynamics (Inutest, CPAH) and sodium segmental handling (sodium distal delivery, distal reabsorption, and fractional excretion) were studied in 9 healthy adults infused with an isotonic amino acid solution and in 6 subjects infused with 0.9% saline for 3 h at 0.2 ml/min/kg. During all tests maximal water diuresis was induced and maintained to effect analysis of sodium segmental transport. Both types of infusion produced a similar expansion of extracellular volume (weight increase, hematocrit fall, suppressed plasma renin activity and plasma aldosterone). The amino acid infusion increased the glomerular filtration rate (GFR) and renal blood flow without modifying the filtration fraction. With saline no hemodynamic modifications were observed. The expansion with saline depressed proximal and distal sodium reabsorption whereas during amino acid infusion sodium distal delivery was unaltered and the significantly increased sodium fractional excretion was sustained only by depressed distal reabsorption. Therefore, in parallel with the GFR increase, closely dependent on renal vasodilatation, the well-known stimulation of sodium cotransport by amino acids is able to antagonize the effects of expansion on the proximal sodium reabsorption. An explanation of glomerular hyperfiltration based on a primary metabolic stimulation of the proximal tubular function is suggested.

Progression of mineral metabolism derangements in childhood chronic renal failure.

2 groups of children affected by different degrees of chronic renal failure (group 1, 55-36 ml/min/1.73 m2; group 2, 35-20 ml/min/1.73 m2 of creatinine clearance) due to tubulo-interstitial disease were studied for one year. The spontaneous evolution of altered mineral metabolism at different levels of glomerular filtration rate (GFR) was aimed at. Parathyroid hormone, vitamin D metabolites and bone mineral content were evaluated. At the end of the year, only a decrease of plasma levels of 1,25(OH)2D in group 1 and a worsening of all mineral metabolism parameters in group 2 were found. The results are consistent with the hypothesis that mineral metabolism derangements progress rapidly after a certain 'threshold' of endocrinologically active renal mass is reached. The falling of plasma 1,25(OH)2D levels below a still undetermined critical value might be assumed as an index of this threshold.

Early childhood hyperkalemia: variety of pseudohypoaldosteronism.

Fractional excretion of electrolytes, renal acidification capacity and the renin-aldosterone system have been studied in 5 non-azotemic children, 19-25 months old, with mineralocorticoid resistant hyperkalemia, discovered in the first month of life. Although fractional potassium excretion was similar in patients and in a group of control healthy children (13.8 +/- 5.2% vs. 8.7 +/- 6.4%) it was inappropriately low in the patients for their higher potassium concentration. Fractional sodium excretion was significantly increased in the patients (1.6 +/- 0.3% vs. 0.67 +/- 0.4, p less than 0.02). Normal net acid and ammonium excretion and intact ability to lower urinary pH during acid loading were observed in all patients. Mean values for plasma aldosterone (37.0 +/- 9.1 vs. 13.9 +/- 11.2 ng/dl), plasma renin activity (12.5 +/- 3.9 vs. 8 +/- 2.8 ng/ml/h) and plasma aldosterone/plasma potassium ratio (7.11 +/- 1.5 vs. 3.08 +/- 1.7) were higher in the patients than in the control subjects (all p less than 0.001). These data support the hypothesis that a partial lack of response of the renal tubule to endogenous mineralocorticoids was present in the patients. This type of pseudohypoaldosteronism is less severe than that described for the classic form and for early childhood renal acidosis.

Renal function in cystic fibrosis.

The effect of saline extracellular volume expansion (4 ml/min/10 kg b.w. X 60 min) on renal function has been studied in patients with cystic fibrosis (CF) and in normal age-matched controls. Basal values for glomerular filtration rate (GFR), renal plasma flow (RPF), tubular sodium and chloride (Na, Cl) handling were similar in both groups. Saline expansion resulted in an increase in GFR and RPF in the CF patients: 127 +/- 18 ml/min/1.73 sqm BSA to 166 +/- 5; p less than 0.001, but not in the control group: 112 +/- 10 to 120 +/- 20. These hemodynamic changes were associated with increased proximal tubular reabsorption of NaCl in the CF patients whereas controls had reduced NaCl reabsorption. Renin and aldosterone levels suggested that increased NaCl reabsorption in CF patients was not secondary to chronic extracellular volume contraction or salt loss. These results support the hypothesis that the renal tubule is involved in the generalised electrolyte transport disorder exhibited in other epithelial structures. This study also indicated that the regulation of renal hemodynamics is altered in CF. The relationship between the disorder of proximal tubular salt handling and changes in renal hemodynamics is not known, but the observed changes imply a tubulo-glomerular feedback mechanism.

Prediction of the progression of renal failure in adult and in pediatric patients with malignant focal glomerulosclerosis.

A retrospective analysis of the progression of renal failure was performed in 6 children and 5 adults with idiopathic nephrotic syndrome unresponsive to steroids and immunosuppressants and with histological findings of focal glomerulosclerosis. We analyzed the linear regression of Ccr and of their logarithmic transformation vs time (months) starting from the time when the first abnormal value was observed (t = 0). The regression analysis was performed at three different times, when Ccr was: 30-20, 20-25 and 10-15 ml/min/1.73 sqm. Extrapolation of each of these lines on the x axis predicted when renal function would be zero. The difference in months, between the predicted and actual time of starting dialysis was prediction error. "r" values were always elevated and statistically significant for both linear and logarithmic regression; there was a large intersubject variability in the rate of loss of renal function but the mean prediction error at various levels of Ccr was within limits clinically acceptable. Moreover its magnitude did not significantly decrease by prolonging the time of observation. This indicates that in this disease the decay of Ccr enters a track which proceeds linearly or logarithmically after the onset of renal failure and no major deviation from the predicted line is to be expected. The good predictability in our study may be attributed to the fact that our patients were homogeneous for a number of factors which may be relevant to progression of the disease. It confirms the view supported by Gretz et al. [1983] that there is a need for stratification of patients in large cohort studies on the predictability of loss of renal function.

Renal tubular acidosis in a case of Shwachman's syndrome.

We describe metabolic acidosis in a 15-month-old girl with clinical features of Shwachman's syndrome. Renal function tests indicated that the patient had type 1 renal tubular acidosis. Based on our findings and other reports of renal tubular dysfunction in patients with Shwachman's syndrome, we conclude that it is important to look for a possible renal tubular defect in this syndrome.