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At least 19 recordsLinked to original sources
PubMed2026

Comprehensive Landscape of Post-Translational Modification Alterations in Nephrolithiasis Revealing Activation of Multiple Cell Death Pathways.

Nephrolithiasis is a common urinary disorder characterized by high prevalence and recurrence, but the molecular mechanisms underlying calcium oxalate (CaOx)-crystal-induced renal injury remain incompletely understood. We applied integrated proteomic, phosphoproteomic, acetylomic, and lactylomic analyses to kidney tissues from a mouse model of CaOx nephrolithiasis followed by bioinformatic analysis and experimental validation. We identified 658 differentially expressed proteins, 735 differential phosphorylation sites, 335 differential acetylation sites, and 113 differential lactylation sites. Functional enrichment indicated immune activation, fibrotic remodeling, and alterations in PI3K-Akt, NOD-like receptor, p53, and Toll-like receptor signaling together with changes in fatty acid degradation, the tricarboxylic acid cycle, and glycolysis. Kinase activity prediction suggested the relative activation of multiple cyclin-dependent kinases. Proteins associated with ferroptosis, autophagy, necroptosis, and pyroptosis, including ACSL4, BNIP3, RIPK3, and GSDMD, showed coordinated abundance and modification changes. Several candidate sites, including MTOR_S1849, GCLM_K94, GCLM_S59, and GSS_K172, were also dysregulated. These data provide a multiomics resource for CaOx nephrolithiasis and identify candidate PTM events and regulatory pathways for future mechanistic validation.

Animals↗
PubMed1978

Hyperglycinuria with nephrolithiasis.

The case of a seven and a half-year-old girl with hyperglycinuria, oxalate nephrolithiasis, and a normal plasma amino acid pattern is presented. Hyperglycinuria amounted to 400 mg of glycine in 24 h urine and the stone was composed of calcium oxalate dihydrate. The metabolic relationship between glycine and oxalate is discussed. It is possible that the association of nephrolithiasis and hyperglycinuria was coincidental, although the case of familial hyperglycinuria with nephrolithiasis reported by De Vries and collaborators and our case suggest the possibility of a relationship between the aforesaid compounds in vivo.

Child↗
PubMed1979

Recurrence of nephrolithiasis. A six-year prospective study.

Retrospective studies of nephrolithiasis tend to overestimate the severity of the disease and mistakenly ascribe benefits to treatment regimens. The results of a three-year study of recurrent nephrolithiasis in three patient groups adhering to a calcium-restricted diet who were treated with phosphate therapy, placebo or diet alone are re-examined at the close of an additional three-year follow-up period. Nearly half the subjects in all groups remained free of stone for the six-year period. A reduction in the need for lithotomies occurred in all groups. The absence of renal calcification at entry into the study as well as increasing age were associated with a marked reduction in stone passage. Drug therapy should probably be avoided in older patients as well as in those who are free of renal calcifications.

Adolescent↗
PubMed1979

Histomorphometric analysis of bone changes in surgically proven primary hyperparathyroidism and nephrolithiasis--the importance of bone biopsy in diagnosis.

The morphologic changes in trabecular bone were studied in 60 patients with surgically proven hyperparathyroidism and in 69 patients with nephrolithiasis. The hyperparathyroid bone lesions showed substantial variation in their extent. Four, typical stages were defined. The structure of trabecular bone remained intact in most cases. Bone turnover is significantly higher in the patients with primary hyperparathyroidism. Fifty percent of all patients with nephrolithiasis had bone changes similar to those found in the surgically proven hyperparathyroidism group. In 50% of so-called asymptomatic cases of hyperparathyroidism, the iliac crest biopsy is a useful supplement to clinical and hormonal data in deciding whether to operate on the parathyroid glands. In about 45% of cases, however, no definite diagnoses is possible. The determination of serum parathyroid hormone in primary hyperparathyroidism has a greater importance for diagnostic purposes than morphologic investigation of the bone biopsy.

Adolescent↗
PubMed1978

Effect of parathyroid extract on renal cyclic AMP excretion in patients with normocalciuric nephrolithiasis.

It is uncertain whether normocalcemic, normocalciuric patients with calcium nephrolithiasis have a disorder of calcium metabolism. We studied the effect of a parathyroid extract (PTE) INFUSION (1.4 U/kg body weight) on the urinary cyclic AMP excretion in 16 such patients. For comparison, we investigated groups of normal individuals and patients with primary hyperparathyroidism, renal insufficiency and different gastrointestinal diseases. The increase of cyclic AMP above basal excretion in patients with nephrolithiasis was only 1.2 +/- 0.3 mumol/h (mean +/- SEM), versus 2.5 +/- 0.5 mumol/h in normal subjects (p less than 0.05) although the basal excretion was similar. Patients with renal insufficiency had low basal excretion of cyclic AMP and little stimulation of excretion by PTH (increase, 0.3 +/- 0.06 mumol). Patients with primary hyperparathyroidism had high baseline cyclic AMP excretion but sub-normal stimulation by PTE (increase, 0.46 +/- 0.13); in contrast, patients with different gastrointestinal disease had high baseline excretion and supranormal stimulation of cyclic AMP excretion (increase, 5.2 +/- 0.6). We speculate that an impaired response to PTH might be involved in the slightly increased urinary calcium excretion in normocalcemic stone formers suggested by others.

Adolescent↗
PubMed1992

Thiazide therapy for ACTH-induced hypercalciuria and nephrolithiasis.

A one-year-old boy presented with hypercalciuria and nephrolithiasis following a course of ACTH therapy for infantile spasms. After a successful cystolithotripsy, therapy with chlorothiazide was followed by regression of the hypercalciuria within 42 months. Neither nephrolithiasis nor nephrocalcinosis recurred. Therapy with thiazides to prevent hypercalciuria caused by ACTH is proposed.

Adrenocorticotropic Hormone↗
PubMed1979

Idiopathic calcium nephrolithiasis. 1. Differences in urine crystalloids, urine saturation with brushite and urine inhibitors of calcification between persons with and persons without recurrent kidney stone formation.

The propensity of urine to promote calcium stone formation was compared in 64 patients with recurrent idiopathic calcium nephrolithiasis and 30 healthy individuals without such a history. The rates of excretion of urine crystalloids, the urine saturation with brushite (CaHPO4-2H2O), the ability of the urine to calcify collagen in vitro, and the concentration of urine inhibitors of collagen calcification were measured. The patients had a reduced urine citrate excretion rate in addition to an increased urine calcium excretion rate, while the rates for urine magnesium, phosphate, uric acid and oxalate were not significantly different in the two groups of subjects. The urine concentration of magnesium, phosphate and uric acid was decreased in the patients because of the higher urine volume. The urine creatinine excretion rate correlated with the rates of excretion of urine calcium, magnesium, phosphate, uric acid and oxalate in both groups, which suggested that increased lean body mass, possibly associated with greater food intake, may be an important determinant of crystalloid excretion. The urine of the patients was significantly more saturated with brushite than the urine of the control subjects and resulted in greater collagen calcification when incubated in vitro. The urine concentration of inhibitors of collagen calcification, however, was not significantly different in the two groups. Thus, the urine of patients with recurrent idiopathic calcium nephrolithiasis is more highly saturated with brushite, largely as a result of an increased urine calcium excretion rate, and contains a lower concentration of magnesium and citrate, substances that tend to prevent the precipitation and growth of crystals in urine.

Adult↗
PubMed1979

[Recent advances in the treatment of nephrolithiasis (author's transl)].

The treatment of nephrolithiasis depends mainly on the type of stone present. Uric acid calculi can be dissolved by oral medication producing alkalinization of the urine. Cystin stones can only rarely be dissolved by oral administration of D-penicillamine. The best and least expensive prophylaxis is a high and constant fluid intake of 600 ml every 4 hours. This way the pathologically increased cystin excretion can be kept soluble. Calcium containing calculi and so-called "infection stones" need surgical intervention. Because of the high recurrence rate of renal stones every indication for an operative procedure has to be considered very carefully. For lasting results elimination of urinary obstruction is necessary. The treatment of choice of patients with staghorn calculus disease is surgical, even in the solitary kidney and in geriatric patients. As recent advances in the operative treatment of nephrolithiasis coagulum pyelolithotomy, intraoperative pyeloscopy, hypothermia and "bench surgery" (extra-corporeal renal surgery) are reviewed. Attempts to dissolve renal calculi by percutaneous nephrostomy as well as extraction of pelvic stones by the same procedure are mentioned. Finally, the importance of postoperative prophylaxis and the progress made in the medical treatment of calcium stones are pointed out.

Calcium↗
PubMed1978

Calcium-uric acid nephrolithiasis.

A small fraction of patients with nephrolithiasis form mixed stones containing calcium and uric acid or pass both calcium and uric acid stones; 23 of 539 patients we have studied fall in this category. These mixed stone formers tend to have unusually frequent stone recurrences. Although the patients are often considered to have a variant of uric acid nephrolithiasis, a high proportion harbor calcium as well as uric acid disorders. The usual treatment for uric acid lithiasis may fail to prevent calcium stone recurrence, unless concomitant calcium disorders are simultaneously corrected. Dual treatment may be very effective in preventing continued stone disease.

Adult↗
PubMed2026

Physiologic age modifies the association between visceral fat predominance and urinary calcium excretion in adults with nephrolithiasis.

Although adiposity is associated with kidney stone disease, the relationship between abdominal fat distribution and urinary calcium excretion remains unclear. We investigated whether the CT-derived visceral-to-subcutaneous fat ratio (VSR) was associated with 24-hour urinary calcium excretion and whether physiologic age modified this association. This retrospective cross-sectional study included 308 adults with nephrolithiasis who underwent preoperative CT, stone removal, and postoperative metabolic evaluation. Participants were stratified into prespecified younger (men aged&#x2009;<&#x2009;50 years and premenopausal women) and older (men aged&#x2009;&#x2265;&#x2009;50 years and postmenopausal women) physiologic-age groups. Multivariable linear regression assessed the association between VSR and urinary calcium excretion and its modification by physiologic age. Results showed that VSR was not associated with urinary calcium excretion in the overall cohort, but its association differed significantly by physiologic age (P for interaction&#x2009;<&#x2009;0.001). Among younger participants, each 1-unit higher VSR was associated with 2.07 mmol/day greater urinary calcium excretion (95% CI, 1.23-2.90), whereas no significant association was observed in the older group. These findings suggest that the metabolic relevance of visceral fat predominance differs by physiologic age, with a significant association observed only in younger adults. Prospective studies are needed to confirm these findings and determine their clinical implications.

Humans↗
PubMed1975

Ureteropelvic junction obstruction in nephrolithiasis. An etiologic factor.

Obstruction is rarely accepted as the sole cause of calculi. We have reviewed 106 cases of nephrolithiasis for which surgery was performed at the St. Luke's Hospital Center during the past ten years. In 17 of these cases, obstruction of the ureteropelvic junction was demonstrated, an incidence of 16 per cent. We propose the theory that too frequently the responsible ureteropelvic junction obstruction goes undetected when a "routine" pyelolithotomy or nephrolithotomy is performed.

Adolescent↗
PubMed1978

Effects of magnesium oxide on the crystallization of calcium salts in urine in patients with recurrent nephrolithiasis.

The effect of oral administration of magnesium oxide on the crystallization in urine of calcium oxalate and brushite was determined in 4 cases of recurrent calcium nephrolithiasis. Each patient was evaluated while on a constant metabolic diet before, during and after therapy with magnesium (1,000 mg. magnesium as magnesium oxide per day). During magnesium therapy urinary hydrogen ion concentration increased by approximately 0.5 unit in all 4 patients and urinary calcium increased about 50 mg. per day in 2. Urinary oxalate decreased significantly in 1 patient and urinary phosphorus was reduced in 2. The urinary activity product ratio of brushite (state of saturation) increased, owing largely to the rise in urinary hydrogen ion concentration but that of calcium oxalate was not changed significantly by magnesium treatment. Although urinary magnesium increased significantly there was no significant change in the urinary formation product ratio (limit of metastability) or the rate of crystal growth of brushite or calcium oxalate. Thus, no beneficial effect of magnesium therapy could be demonstrated in this short-term study.

Administration, Oral↗
PubMed1975

Pediatric nephrolithiasis.

The management of 78 children with upper urinary calculi is described. Boys outnumbered girls by a ratio of 2 to 1. Two-thirds of the patients had identifiable metabolic causes, while the remaining third had infected renal lithiasis. In this latter group, all patients had had multiple urologic procedures, urinary infection, and stasis with diversionary and indwelling drainage devices. Contrary to earlier views, idiopathic renal lithiasis with or without hypercalciuria was the most common metabolic form of nephrolithiasis in children. Sixty-seven patients (86 per cent) were followed for an average of 7 1/2 years. With appropriate therapy, stone disease became inactive in 70 per cent of the children. The remaining 30 per cent continued with active disease--5 died of renal failure and 1 has received a renal allograft. Stone formation may be regarded as a solitary complication or one of several manifestations of a large number of underlying disorders. Along with a thorough search for etiologic factors there must be an equally aggressive therapeutic effort. Because the disease is ofter sporadic, careful long-term followup of the patients with active as well as those with inactive stone disease is mandatory.

Acidosis, Renal Tubular↗
PubMed1979

Urinary saturation measurements in calcium nephrolithiasis.

Urinary saturation with respect to calcium oxalate monohydrate was measured in 111 consecutive patients with calcium nephrolithiasis. Each patient also was evaluated by a detailed conventional metabolic protocol. Patients with idiopathic hypercalciuria produced abnormally oversaturated urine more frequently than normal subjects and normocalciuric patients, but normocalciuric patients had unexpectedly high levels of urine saturation. Measuring levels of calcium concentration, oxalate concentration, or the chemical concentration product of calcium and oxalate in urine did not predict oversaturation. During thiazide treatment, saturation level tended to fall if it was initially elevated, whether the patient was hypercalciuric or not. Patients whose urine was not remarkably oversaturated showed no tendency to elaborate even less saturated urine during thiazide treatment; instead, the average calcium oxalate saturation level remained constant. Direct urine saturation measurements can detect a small but significant number of normocalciuric patients who have marked oversaturation with respect to calcium oxalate and appear to benefit from treatment.

Calcium↗
PubMed1978

Reduced red blood cell carbonic anhydrase activity in a patient with nephrolithiasis.

Low levels of red blood cell (RBC) carbonic anhydrase (CA) activity in hemoglobin-free hemolyzate (HFH) were found in 2 children with nephrolithiasis when compared to age-matched controls. The lowest levels were consistently found over a two year period in a 6 1/2 year old boy (U.P.) whose renal calculi contained uric acid, ammonia, calcium carbonate and oxalate. His RBC CA values ranged from 1.4-2.7 U/g Hb compared with levels of 3.9-5.3 U/g Hb in control subjects. Statistical comparisons of the mean values for U.P., 2.06 U/g Hb, and his age-matched control subjects, 4.46 U/g Hb, revealed a significant difference (P = less than 0.001). Similar reductions in RBC CA activity were found in his father--2.0 and 2.1 U/g Hb compared with 3.3 and 3.9 U/g Hb in adult controls. HFH CA activity was not decreased in the mother or sister. Polyacrylamide gel electrophoresis of HFH from 4 of the children and the father of U.P. was abnormal. However, this abnormal electrophoretic pattern could only be demonstrated when the gel was run for 120 minutes and not when it was run for 80 or 160 minutes. We have identified a patient and his father with low levels of RBC CA activity.

Adolescent↗
PubMed1992

Hyperparathyroidism: cause or consequence of recurrent calcium nephrolithiasis?

Primary hyperparathyroidism (PHP) might be characterized by either prevailing bone or renal stone patterns with different metabolic features. To explore the possibility of different hormonal patterns we studied 129 patients with PHP: 95 stone formers (SF) and 34 nonstone formers (NSF). Females prevailed over males in both groups. Severe and specific bone lesions were more evident in NSF than SF. Parathyroid gland histology displayed a prevalence of adenoma in NSF, whereas isolated hyperplasia prevailed in SF. SF had lower levels of serum Ca, urinary Ca, ALP and serum PTH than NSF. As expected serum 1,25-dihydroxyvitamin D [1,25(OH)2 D] levels were greater in both groups of patients than in controls but we found no difference between the two groups. 25-Hydroxyvitamin D was neither increased with respect to controls nor different between groups. We conclude that patients with PHP may represent well separated metabolic and clinical entities, but we cannot confirm that serum 1,25(OH)2D levels play a key role in discriminating the different clinical features. In addition, the findings of predominant parathyroid hyperplasia in SF and the clinical evidence of recurrent hyperparathyroidism only in these patients suggest the possibility that the endocrine disorder might be the consequence over time rather than the cause of nephrolithiasis.

Adult↗