Nephrocalcinosis

Nephrolithiasis is a prevalent condition with a high morbidity. Although dozens of monogenic causes have been identified, the fraction of single-gene disease has not been well studied. To determine the percentage of cases that can be molecularly explained by mutations in 1 of 30 known kidney stone genes, we conducted a high-throughput mutation analysis in a cohort of consecutively recruited patients from typical kidney stone clinics. The cohort comprised 272 genetically unresolved individuals (106 children and 166 adults) from 268 families with nephrolithiasis (n=256) or isolated nephrocalcinosis (n=16). We detected 50 likely causative mutations in 14 of 30 analyzed genes, leading to a molecular diagnosis in 14.9% (40 of 268) of all cases; 20 of 50 detected mutations were novel (40%). The cystinuria gene SLC7A9 (n=19) was most frequently mutated. The percentage of monogenic cases was notably high in both the adult (11.4%) and pediatric cohorts (20.8%). Recessive causes were more fre...

Adenine phosphoribosyltransferase (APRT) deficiency, cystinuria, Dent disease, familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC), and primary hyperoxaluria (PH) are rare but important causes of severe kidney stone disease and/or chronic kidney disease in children. Recurrent kidney stone disease and nephrocalcinosis, particularly in pre-pubertal children, should alert the physician to the possibility of an inborn error of metabolism as the underlying cause. Unfortunately, the lack of recognition and knowledge of the five disorders has frequently resulted in an unacceptable delay in diagnosis and treatment, sometimes with grave consequences. A high index of suspicion coupled with early diagnosis may reduce or even prevent the serious long-term complications of these diseases. In this paper, we review the epidemiology, clinical features, diagnosis, treatment, and outcome of patients with APRT deficiency, cystinuria, Dent disease, FHHNC, and PH, with an emphasis on childhood manifestations.

We noted microscopic haematuria in children with cystinosis. To investigate this we studied urinary calcium excretion and undertook renal ultrasound scans. Most patients had elevated urinary calcium excretion and all had abnormal appearances on ultrasound scan, ranging from increased cortical echogenicity only to those with increased cortical and medullary echogenicity. The ultrasound scan appearance was graded and correlated with laboratory parameters. It remains unclear as to the aetiology of the ultrasound findings and whether they are a consequence of treatment or a hitherto unrecognised feature of the disease.

The primary disorders of 50 children with increased renal medullary echogenicity on renal ultrasound were studied; 28 girls and 22 boys aged from 1 month to 16 years were classified into four groups based on underlying disease and ultrasound findings. Group 1 was composed of 17 patients with distal renal tubular acidosis (34%); intense echoes throughout the pyramid were predominant. Group 2 consisted of 14 patients with vitamin D toxicity (28%) and an intense echogenic rim around the pyramids. Group 3 included 10 patients with different types of tubulopathies. A slight hyperechogenic rim around the sides and tip of the medullary pyramids was detected. Group 4 was made up of 9 patients with rare underlying conditions. Abdominal X-rays detected medullary calcinosis in only 12 (24%) of the total 50 patients. Ultrasonography appears to be an important tool in the early diagnosis of increased renal medullary echogenicity and medullary nephrocalcinosis.

Primary hyperoxaluria type 1 [PH1] is an autosomal recessive disorder caused by a deficiency of alanine-glyoxylate aminotransferase AGT, which is encoded by the AGXT gene. We report an Indian family with two affected siblings having a novel mutation in the AGXT gene inherited from the parents. The index case progressed to end stage renal disease at 5 months of age. His 4 month old sibling is presently under follow up with preserved renal function.

Magnesium has evolved as a drug with diverse clinical applications. Mg++ is an important caution and its homeostasis is very important for normal body functioning. The physiological role of Mg is due to its calcium channel blocking properties at smooth muscle, skeletal muscle and conduction system levels. The analgesic properties are due to NMDA receptor blocking action. Mg++ is beneficial in acute Myocardial Infarction, protection during open heart surgery and treatment and prevention of heart rhythm disturbances. Mg has an established role in the management of preeclampsia and eclampsia. Magnesium prevents or controls convulsions by blocking neuromuscular transmission and decreasing the release of acetylcholine at the motor nerve terminals. The use of MgSO4 in treating tetanus and acute asthma is established. In conclusion, Mg is a cost effective, widely used drug with multidisciplinary applications. Its majority of physiological effects are attributed to calcium channel blocking ...

Enamel-renal syndrome (ERS) is a rare manifestation of nephrocalcinosis that has been associated with generalized enamel hypoplasia. The purpose of this paper was to describe, for the first time, the association of enamel-renal syndrome with severe localized periodontal bone loss. A 13-year-old boy presented with: generalized hypoplastic enamel; intrapulpal calcifications; retention of primary teeth; delayed eruption of permanent teeth; enlarged dental-follicles; misshaped roots of permanent teeth; gingival overgrowth; severe localized alveolar bone loss; and severe malocclusion. His parents were first cousins, suggesting autosomal recessive inheritance. Further studies are necessary to clarify whether the etiology of the oral disturbances relates to the genetic defect in the dental tissue or to the continuous metabolic distress associated with renal dysfunction. Nevertheless, since nephrocalcinosis is often asymptomatic, dentists should refer children with generalized enamel hypopl...

Background: Hyperoxaluria may be either inherited or acquired. Primary Hyperoxaluria (PH) is a rare autosomal recessive disease characterized by increased endogenous oxalate production and accumulation in renal and extrarenal tissues. The excess oxalate is excreted in the urine and frequently patients with PH present signs or symptoms related to kidney stones and progressive nephrocalcinosis.

Background: Hyperoxaluria has been incriminated to account for the increased incidence of urolithiasis or nephrocalcinosis in patients with cystic fibrosis (CF). Hyperoxaluria presumably is caused by fat malabsorption and the absence of such intestinal oxalate-degrading bacteria as Oxalobacter formigenes. To better elucidate its pathophysiological characteristics, we prospectively studied patients with CF by determining these parameters and performing renal ultrasonography twice yearly. Methods: In addition to routine tests in urine (lithogenic and stone-inhibitory substances), the presence of O formigenes was tested in stool, plasma oxalate was measured, and a [13C2]oxalate absorption test was performed in 37 patients with CF aged 5 to 37 years (15 females, 22 males) who were constantly hyperoxaluric before the study. Results: Hyperoxaluria (oxalate, 46 to 141 mg/1.73 m2/24 h [0.51 to 1.57 mmol/1.73 m2/24 h]; normal, <45 mg/1.73 m2/24 h [<0.5 mmol/1.73 m2/24 h]) was now found in 24 patients (64.8%). Plasma oxalate levels were elevated in 6 patients (7.92 to 19.5 μmol/L; normal, 6.3 ± 1.1 μmol/L). Oxalobacter species were detected in only 1 patient. Intestinal oxalate absorption was elevated (11.4% to 28.5%; normal, <10%) in 23 patients. Hypocitraturia was present in 17 patients (citrate, 0.35 to 2.8 g/1.73 m2/24 h [0.2 to 1.1 mmol/1.73 m2/24 h]; normal female, >2.8 mg/1.73 m2/24 h [>1.6 mmol/1.73 m2/24 h]; male, >3.3 mg/1.73 m2/24 h [>1.9 mmol/1.73 m2/24 h]). Urine calcium oxalate saturation was elevated in 17 patients (5.62 to 28.9 relative units; normal female, <5.5 relative units; male, <6.3 relative units). In 16% of patients, urolithiasis (n = 2) or nephrocalcinosis (n = 4) was diagnosed ultrasonographically. Conclusion: Absorptive hyperoxaluria and hypocitraturia are the main culprits for the increased incidence of urolithiasis and nephrocalcinosis in patients with CF. We advocate high fluid intake, low-oxalate/high-calcium diet, and alkali citrate medication, if necessary. Additional studies are necessary to determine the influence of Oxalobacter species or other oxalate-degrading bacteria on oxalate handling in patients with CF.

Glomerular lesions secondary to calcium deposition in sarcoidosis have not been previously described, to our knowledge. Five renal biopsy specimens from four patients with sarcoidosis were studied by light, electron, and immunofluorescence microscopy. In addition to interstitial granulomatous nephritis and nephrocalcinosis, which were seen in all cases, segmental glomerular lesions characterized by marked thickening and wrinkling of the glomerular capillary walls and basophilic appearance of the altered basement membranes were present in three of the cases. Electron microscopic examination of the lesions revealed dramatic alteration of the glomerular ultrastructure. Numerous single and coalescent calcific microspherules were present within the basement membrane, the paramesangial zone, and the mesangium. The findings of immunofluorescence were noncontributory. The structural alterations caused by calcinosis of the glomerulus may be responsible for some of the frequent renal function...