Mild Idiopathic Infantile Hypercalcemia-Part 2: A Longitudinal Observational Study.

CONTEXT: Idiopathic infantile hypercalcemia (IIH) is an uncommon disorder with variable clinical features. The natural history and response to dietary calcium and vitamin D restriction in IIH remains unclear. OBJECTIVE: The aim of this study is to describe the clinical and biochemical response to dietary calcium and vitamin D restriction in a genetically characterized cohort of mild IIH. METHODS: This is a longitudinal, observational cohort study of 20 children with mild IIH monitored for a median of 21months. Biochemical measures, dietary assessment, and yearly renal ultrasound results, since the time of diagnosis, were obtained and assessed prospectively every 4 to 6 months. RESULTS: Median age at initial diagnosis was 4.5 months. Median levels of serum calcium (2.82 mmol/L) and 1,25 (OH)2D (192 pmol/L) were elevated, whereas serum PTH was reduced (10 ng/L). Urinary calcium:creatinine ratio was elevated for some, but not all individuals (median 1.49 mmol/mmol). All patients who were managed with a low-calcium diet showed an improvement in serum and urinary calcium measures, but the serum concentration of 1,25 dihydroxyvitamin D (1,25(OH)2D) and 1,25(OH)2D/PTH ratio remained elevated. In 2 of the 11 subjects, renal calcification worsened. There were no differences in response between individuals with CYP24A1 or SLC34A1/A3 variants. CONCLUSION: The clinical presentation of mild IIH is variable, and dietary calcium and vitamin D restriction does not consistently normalize elevated 1,25(OH)2D concentrations or prevent worsening of renal calcification in all cases. Therapeutic options should target the defect in vitamin D metabolism.

Consumption of krill protein concentrate prevents early renal injury and nephrocalcinosis in female Sprague-Dawley rats.

Female Sprague-Dawley rats provide an animal model for studying the role of nutrition in renal health due to their sensitivity to diet-induced alterations in kidney function. Nephrocalcinosis, a common renal abnormality found in rats, has been implicated in subsequent renal failure. Simple dietary manipulations, such as changing the source of dietary protein, may influence nephrocalcinosis. This study evaluates the consumption of krill protein concentrate (KPC), a novel and high-quality protein, on renal and bone health. Young female Sprague-Dawley rats (n = 10/group) were individually housed in metabolic cages and fed ad libitum diets consisting of 10% crude protein supplied as KPC or casein for 4 weeks. Diets were isocaloric, isonitrogenous, and matched for calcium (Ca) and phosphorus (P). Urinary n-acetyl glucosaminidase (NAG) was measured and kidney histology performed to assess kidney damage. Biomarkers of kidney function were determined by calorimetric assays. Ca and P balance and bone concentrations were measured using inductively coupled plasma mass spectrometry. Femoral strength was determined by three-point bend testing. Rats fed KPC had lower (P = 0.005) urinary NAG levels and minimal microtubular Ca deposition compared to rats fed casein. There was a tendency (P < 0.06) for higher glomerular filtration rates and lower proteinuria, and higher (P = 0.03) urinary output in rats fed KPC compared to casein. There were no differences in Ca and P balance or bone measurements of total bone mineral content, Ca, P or strength between rats fed KPC and casein. Based on the study results, KPC prevented early renal injury leading to nephrocalcinosis and potential bone loss.

A randomized trial of low-animal-protein or high-fiber diets for secondary prevention of calcium nephrolithiasis.

BACKGROUND: The purpose of this trial was to evaluate the efficacy of a low-animal-protein diet (LAPD) or a high-fiber diet (HFD) for the prevention of calcium nephrolithiasis recurrence. METHODS: We conducted a 4-year randomized trial comparing the effect of 2 diets in 175 idiopathic calcium stone formers. Fifty-five were assigned to a LAPD (<13% of total energy derived from protein), 60 were assigned to a HFD (>25 g/day fiber) and 60 were placed on a normal diet (control group). The primary outcome measure was the time to the first recurrence of calcium nephrolithiasis. Daily urine compositions were analyzed at baseline, at month 4 (M4), M12, M24, M36 and M48. RESULTS: Seventy-three patients completed the trial (23 in the LAPD group, 27 in the HFD group and 23 in the control group). Recurrence was 48% (11/23) in the LAPD group, 63% (17/27) in the HFD group and 48% (11/23) in the control group (p = not significant). During follow-up, urinary calcium levels and other urine parameters did not change significantly in the 3 groups, except for a significant decrease in 24-hour urinary sulfate in the LAPD group. CONCLUSIONS: In idiopathic calcium stone formers, neither a LAPD nor a HFD appeared to provide protection against recurrence.

[Experimental-clinical substantiation of the diet therapy with zosterin in kidney diseases]. / Eksperimental'no-klinicheskoe obosnovanie dietoterapii s vkliucheniem zosterina pri zabolevaniiakh pochek.

The results of enterosorbent of marine origin zoosterol application under nephropathy are cited. Detoxicational, lipid corregated action of zoosterol was revealed as a result of experimental researches on nephrocalcinosis model, but calcium accumulation was observed in animals' kidney tissue. Clinical examinations including zoosterol application and dietotheraphy showed the decreasing of heightened calcium level in serum and urine, cholesterol and triglycerides, stabilization of membranodestructive processes in urinary excretive system for patients with chronic pyelonephritic.

Neonatal nephrocalcinosis in association with glucose-galactose malabsorption.

We report a case of severe nephrocalcinosis related to hypercalcaemia in a newborn with glucose-galactose malabsorption. He presented with poor growth and was noted to have polyuria, which was later recognised to be severe watery diarrhoea. We discuss the possible aetiological factors for nephrocalcinosis in this condition.

Nephrocalcinosis in three siblings with idiopathic hypercalciuria.

Idiopathic hypercalciuria (IH) associated with nephrocalcinosis was found in three of six siblings. After the three affected children were maintained on a low-calcium diet, they demonstrated increasing hypercalciuria, parathyroid hormone, and vitamin D3 levels. An oral calcium loading test was not necessary to diagnose renal IH. During treatment with hydrochlorothiazide, the calcium excretion was normalized. These patients are remarkable because nephrocalcinosis is generally regarded as a rare complication of renal IH. Moreover, the fact that three of six siblings are affected raises the question of whether the renal form of IH is genetically distinct from other forms of IH.

Effects of mineral composition of drinking water on risk for stone formation and bone metabolism in idiopathic calcium nephrolithiasis.

1. To assess whether the mineral content of drinking water influences both risk of stone formation and bone metabolism in idiopathic calcium nephrolithiasis, 21 patients were switched from their usual home diets to a 10 mmol calcium, low-oxalate, protein-controlled diet, supplemented with 21 of three different types of mineral water. Drinking water added 1, 6 and 20 mmol of calcium and 0.5, 10 and 50 mmol of bicarbonate respectively to the controlled diet. 2. The three controlled study periods lasted 1 month each and were separated by a 20 day washout interval. Blood and urine chemistries, including intact parathyroid hormone, calcitriol and two markers of bone resorption, were performed at the end of each study period. The stone-forming risk was assessed by calculating urine saturation with calcium oxalate (beta CaOx), calcium phosphate (beta bsh) and uric acid (beta UA). 3. The addition of any mineral water produced the expected increase in urine output and was associated with similar decreases in beta CaOx and beta UA, whereas beta bsh varied marginally. These equal decreases in beta CaOx, however, resulted from peculiar changes in calcium, oxalate and citrate excretion during each study period. The increase in overall calcium intake due to different drinking water induced modest increases in calcium excretion, whereas oxalate excretion tended to decrease. The changes in oxalate excretion during any one study period compared with another were significantly related to those in calcium intake. Citrate excretion was significantly higher with the high-calcium, alkaline water. 4. Parathyroid hormone, calcitriol and markers of bone resorption increased when patients were changed from the high-calcium, alkaline to the low-calcium drinking water. 5. We suggest that overall calcium intake may be tailored by supplying calcium in drinking water. Adverse effects on bone turnover with low-calcium diets can be prevented by giving high-calcium, alkaline drinking water, and the stone-forming risk can be decreased as effectively as with low-calcium drinking water.

Inhibitory effect of high protein intake on nephrocalcinogenesis in female rats.

Increased intakes of protein have been shown to reduce kidney calcification (nephrocalcinosis) in female rats. Two questions were addressed in the present study. First, can protein-induced inhibition of nephrocalcinosis be demonstrated when the diets used are balanced for calcium, magnesium and phosphorus in the added protein? Second, can the protein effect be explained by the frequently observed magnesiuria after giving high-protein diets? Nephrocalcinosis was induced in female rats by giving purified diets containing 151 g casein/kg and either an increased concentration of P (6 v. 2 g/kg) or a decreased concentration of Mg (0.1 v. 0.4 g/kg). To these diets 151 g ovalbumin/kg was added at the expense of glucose, and the diets were balanced for Ca, Mg and P in ovalbumin. The diets were given for 29 d. In rats fed on the diet containing 151 g protein/kg, an increased intake of P or a decreased intake of Mg caused nephrocalcinosis as measured chemically by analysis of kidney Ca as well as histologically by scoring kidney sections stained according to Von Kossa's method. The addition of ovalbumin to the diet prevented the induction of nephrocalcinosis. High P intake and low Mg intake with the low-protein diets induced enhanced loss of albumin in urine, suggesting that nephrocalcinosis caused kidney damage. Increased protein intake with a non-calcinogenic diet also caused increased albumin excretion in urine. Irrespective of the composition of the background diet, increased protein intake caused increased urinary excretion of Mg. When all dietary groups were considered, differences in nephrocalcinosis and urinary Mg output were not proportionally related.

The influence of dietary magnesium on reduction of nephrocalcinosis in rats fed purified diet.

The severity of nephrocalcinosis in female Colworth Wistar rats fed on a standard purified diet was reduced by increasing the magnesium content of the diet; both its incidence and severity could be increased in males of the same strain by lowering the dietary magnesium level.

Effect of dietary phosphorus restriction on the kidneys of cats with reduced renal mass.

Cats with reduced renal mass were fed a phosphorus-restricted diet (0.24% P, dry weight) or a normal phosphorus diet (1.56% P, dry weight) for 6 5 to 343 days. Renal function was determined biweekly by blood urea nitrogen and plasma creatinine measurements and by initial and terminal inulin clearance procedures. Neither diet caused a significant change in renal function during the study. However, histologic examination of kidneys obtained at necropsy clearly separated the cats on the basis of dietary phosphorus. The kidneys from cats fed the normal phosphorus diet had mineralization, fibrosis, and mononuclear cell infiltration, whereas the kidneys from cats fed the phosphorus-restricted diet had little or no changes.