Progression Of Nephrolithiasis Research Articles

Troublesome Teeth, Search for Stones – Enamel-Renal Syndrome

Background: Enamel-renal syndrome (ERS), is a rare autosomal recessive disorder involving family with sequence similarity 20 member A (FAM20A) gene. This unique syndrome is characterized by severe enamel hypoplasia, intrapulpal calcification, nephrocalcinosis, or nephrolithiasis. This case report highlights the early presentation and incidental detection of chronic kidney disease (CKD) in a young child with enamel defects. Clinical Description: A 10-year-old girl, with no significant past or family history, presented with delayed tooth eruption and abnormal shaped teeth. She was detected to have generalized gingival hyperplasia and multiple unerupted teeth. Suspecting amelogenesis imperfecta, she was screened for coexisting systemic conditions. On evaluation, abdominal ultrasound demonstrated bilateral nonobstructive nephrolithiasis. Further renal workup done showed an abnormal creatinine (stage 2 CKD) and mild metabolic acidosis. Reduced urinary citrate excretion with no evidence of hypercalciuria was noted on extensive urine assessment. Genetic testing revealed a novel pathogenic variant in FAM20A, confirming the diagnosis of ERS. Management: The child was initiated on citrate supplements, salt restriction, and adequate hydration. She was advised of dental interventions, including pulp therapy and full-coverage restoration of decayed teeth. The family was counseled about the need for close monitoring of growth, renal function, and progression of nephrolithiasis. Conclusion: Prompt screening for renal associations in oro-dental and systemic disease must be undertaken to ensure early detection of kidney disease and timely institution of appropriate treatment. In children diagnosed to have kidney involvement, the importance of regular follow-up with clinical, biochemical, and imaging modalities, even during adulthood, must be emphasized.

Genetic polymorphisms of human transcription factor-7 like 2 (TCF7L2), β-defensin (DEFB1) and CD14 genes in nephrolithiasis patients

BackgroundIt is assumed that genetic factors play crucial role in nephrolithiasis. The present study was conducted to explore the role of Human Transcription Factor-7 like-2 (TCF7L2) β-defensin (DEFB1) and CD14 gene polymorphism in development and progression of nephrolithiasis. MethodsThe genotypes of TCF7L2, DEFB1 and CD14 polymorphism were determined in 240 nephrolithiasis patients and 240 healthy controls by restriction digestion method of PCR. The levels of serum TCF7L2, DEFB1, CD14, uric acid and other biochemical parameters were measured both in nephrolithiasis patients and healthy control. ResultsThe patients and control groups showed 30% and 50% 1654 AA DEFB1 genotype respectively. The Allele frequency in case of patient's group was 63.67% while in control group it was 36.33%. The mean serum DEFB1 levels of the patients and control groups attained were 115.66 and 239.43 pg/mL respectively. The allele frequency of TCF7L2 in patients and controls were 44.17% and 70.0% for C-allele, 55.83% and 30.00% for T-allele respectively. The mean of serum TCF7L2 levels were significantly decreased in patients compared to control group. ConclusionsThe present findings are first of its class that validates a considerable connection of DEFB1 and TCF7L2 gene polymorphisms with nephrolithiasis and could probably act as indicators to estimate the risk associated to nephrolithiasis.

Natural History of Asymptomatic Renal Stones and Prediction of Stone Related Events

The appropriate management for asymptomatic renal stones remains unclear. We assessed the natural history and progression rate of such stones and identified clinical factors associated with an increased risk of stone related events. We retrospectively reviewed the medical records of 201 male and 146 female patients with asymptomatic renal stones. It was recommended that patients be followed every 6 months. Mean followup was 31 months (range 6 to 180). Patients were divided into 2 groups by stone related events, including spontaneous stone passage, flank pain, stone growth or the need for intervention during followup. Spontaneous passage occurred in 101 patients (29.1%). Of the patients 186 (53.6%) and 161 (46.4%) did and did not have stone related events, respectively. Of the whole cohort 85 patients (24.5%) required intervention but only 4.6% needed surgery. At 19 months after diagnosis 50% of the patients had a symptom. Those with stone related events were more likely to be younger (mean ± SD age 46.6 ± 12.7 vs 49.3 ± 12.6 years) and male, and have a stone history (p = 0.047, 0.017 and 0.014, respectively). Male gender significantly decreased the probability of freedom from stone related events (log rank test p = 0.0135) and it was an independent predictor of stone related events (HR 1.521, p = 0.009). Younger patients, and those with smaller stones and no stone growth were more likely to experience spontaneous passage and less likely to undergo intervention (each p <0.05). Asymptomatic renal stones can be followed safely but long-term followup is necessary. Periodic followup and early intervention should be recommended in patients with risk factors.

A Prospective, Randomized Trial of Management for Asymptomatic Lower Pole Calculi

We determined the natural course and compared the deleterious effects in kidneys of shock wave lithotripsy, percutaneous nephrolithotomy and observation for asymptomatic lower caliceal stones. Between April 2007 and August 2008 patients with asymptomatic lower caliceal calculi were enrolled in the study. To assess stone status noncontrast abdominal helical computerized tomography was done 3 and 12 months after intervention. All patients were evaluated by dimercapto-succinic acid renal scintigraphy 6 weeks and 12 months after intervention. A total of 94 patients were prospectively randomized to percutaneous nephrolithotomy (31), shock wave lithotripsy (31) and observation (32). Mean +/- SD followup was 19.3 +/- 5 months (range 12 to 29). In the percutaneous nephrolithotomy group all patients were stone-free at month 12. Scintigraphy revealed a scar in 1 patient (3.2%) on month 3 followup imaging. In the shock wave lithotripsy group the stone-free rate was 54.8%. Scintigraphy revealed scarring in 5 patients (16.1%). In the observation group 7 patients (18.7%) required intervention during followup. Median time to intervention was 22.5 +/- 3.7 months (range 18 to 26). One patient (3.1%) had spontaneous stone passage. Scintigraphy did not reveal scarring in any patient. Stone related events were noted in more than 20% of patients with asymptomatic lower caliceal stones observed expectantly. To manage lower caliceal stones percutaneous nephrolithotomy has a significantly higher stone-free rate with less renal scarring than shock wave lithotripsy. Thus, patients with asymptomatic lower caliceal stones must be informed in detail about all management options, especially focusing on percutaneous nephrolithotomy with its outstanding outcome.

Lipid peroxidation is not the underlying cause of renal injury in hyperoxaluric rats

Hyperoxaluria is a major risk factor of calcium oxalate stone disease and renal injury is thought to be a significant initiating event. However, the relationship among oxidative stress, renal tubule injury and hyperoxaluria in the progression of nephrolithiasis is unclear, especially in animal models. In the current study, we assess the role of oxidative stress in renal tubular damage in a rat model of chronic hyperoxaluria (HYP) and chronic renal failure induced by hyperoxaluria (HRF) compared to control rats. Urinary excretion of renal tubular enzymes, including lactate dehydrogenase (LDH), alkaline phosphatase (AP), N-acetyl-beta-D-glucosaminidase (NAG), and alpha- and mu-glutathione-S-transferase (alpha-GST and mu-GST, respectively) was quantified in four groups of Sprague-Dawley rats. The study included normal controls, those made hyperoxaluric with ethylene glycol administration (HYP), unilateral nephrectomized controls, and unilateral nephrectomized rats administered ethylene glycol (HRF). Levels of catalase, superoxide dismutase (SOD), glutathione peroxidase (GP), and glutathione transferase (GST) in the renal cortex were measured after 4 weeks and lipid peroxidation was assessed by measuring 8-isoprostane in the urine and lipid hydroperoxide in the renal cortex. Urinary excretion of NAG, AP, and LDH was elevated after 2 and 4 weeks in the HYP and HRF groups. Urinary levels of mu-GST, a marker of distal tubule damage, were elevated in HRF rats after 4 weeks. alpha-GST levels were similar between control and HYP rats but were lower in HRF rats. Levels of catalase, SOD, GP, and GST in the renal cortex were similar among control, HYP, and unilateral nephrectomized control rats, but were attenuated in the HRF rats after 4 weeks. Renal cortical content of lipid hydroperoxide and urinary 8-isoprostane levels were similar among all groups after 4 weeks. Ethylene glycol-induced hyperoxaluria in Sprague-Dawley rats is accompanied by enzymuria, which is suggestive of renal tubular damage. The antioxidant capacity of the renal cortex in HYP rats is similar to that of control rats after 4 weeks of treatment; however, this capacity is significantly attenuated in rats that are in renal failure induced by hyperoxaluria, although significant lipid peroxidation is not evident. These results suggest that lipid peroxidation is not the underlying cause of renal injury in hyperoxaluric rats.

Credentials of Spirulina diet on stability and flux related properties on the biomineralization process during oxalate mediated renal calcification in rats

High Spirulina diet is a potential risk factor for nephrolithiasis since it has the capacity to increase urinary oxalate and uric acid level, facilitating lithogenesis. Our aim was to identify the effect of Spirulina diet during hyperoxaluric condition in Wistar albino rats. The animals were divided into four groups: control (Gl, n=6); ethylene glycol (EG) induced (G2, n=6); EG+Spirulina (G3, n=6); Spirulina alone (G4, n=6). EG at 0.75% was administered to G2 and G3 through drinking water for 4 weeks and Spirulina 1500 mg/kg feed was administered to G3 and G4. Urinary parameters like oxalate, uric acid, calcium, urea, and creatinine (P<0.001) were found increased after Spirulina diet under hyperoxaluric conditions compared to the same without Spirulina diet. Similarly the BUN, plasma contents of uric acid, urea, creatinine (P<0.001) were found to be raised in G3. The renal and RBC GSH levels, as estimated by HPLC, seemed decreased when compared to G2. The present study shows that free radicals aid in the progression of nephrolithiasis. The crystal deposition was found to be high in the renal cells of G3 than G2 and TEM revealed damage in renal cell of G3 implying that the disease deteriorates by free radical injury. In contrast the Spirulina diet alone (G4) did not induce any features relating to stone forming condition suggesting that free radical release might have been suppressed due to enrichment of dietary antioxidants and vitamins. Thus the present investigation demonstrates that during hyperoxaluric conditions the Spirulina diet must possibly be avoided and can be considered in normal subjects checked for family history of renal stone deposition.

Progression of nephrolithiasis: long-term outcomes with observation of asymptomatic calculi.

Observation is often recommended for patients presenting with asymptomatic renal calculi. This study evaluated the natural history of asymptomatic calculi and the risk of progression of disease. We conducted a retrospective evaluation of 300 male patients average age 62.8 years who were followed for a mean of 3.26 years for asymptomatic renal calculi in an outpatient urology clinic. At presentation, the mean cumulative stone diameter was 10.8 mm; 56% were lower-pole stones, and 48% of the patients had multiple calculi. Patients underwent annual radiographic imaging and clinic visits with standardized questions regarding the development of symptoms or complications from calculi. Progression of disease was defined as the need for surgical intervention, the development of pain, or stone growth on serial imaging. Overall, 77% of patients experienced disease progression, with 26% requiring surgical intervention. Stone size was positively associated with progression: those with an isolated stone >/=4 mm on presentation were 26% more likely to fail observation than patients with smaller solitary calculi (P = 0.012). Stone growth was less common in those with upper-pole and middle-pole stones (47% v 61%) for lower-pole stones; P = 0.002). Urine uric acid concentration correlated positively with the rate of stone growth (P = 0.05). Likewise, serum uric acid concentration predicted stone growth (odds ratio = 3.6). Stratification of risk of progression according to presenting stone size, location, and composition may facilitate discussions with the patient regarding the alternatives of observation versus intervention. Specifically, small non-uric acid calculi in the upper pole may be most amenable to observation.

Progression of Nephrolithiasis: Long-Term Outcomes with Observation of Asymptomatic Calculi

Background and Purpose: Observation is often recommended for patients presenting with asymptomatic renal calculi. This study evaluated the natural history of asymptomatic calculi and the risk of progression of disease. Patients and Methods: We conducted a retrospective evaluation of 300 male patients average age 62.8 years who were followed for a mean of 3.26 years for asymptomatic renal calculi in an outpatient urology clinic. At presentation, the mean cumulative stone diameter was 10.8 mm; 56% were lower-pole stones, and 48% of the patients had multiple calculi. Patients underwent annual radiographic imaging and clinic visits with standardized questions regarding the development of symptoms or complications from calculi. Progression of disease was defined as the need for surgical intervention, the development of pain, or stone growth on serial imaging. Results: Overall, 77% of patients experienced disease progression, with 26% requiring surgical intervention. Stone size was positively associated with progression: those with an isolated stone ≥4 mm on presentation were 26% more likely to fail observation than patients with smaller solitary calculi (P = 0.012). Stone growth was less common in those with upper-pole and middle-pole stones (47% v 61%) for lower-pole stones; P = 0.002). Urine uric acid concentration correlated positively with the rate of stone growth (P 5 0.05). Likewise, serum uric acid concentration predicted stone growth (odds ratio = 3.6). Conclusions: Stratification of risk of progression according to presenting stone size, location, and composition may facilitate discussions with the patient regarding the alternatives of observation versus intervention. Specifically, small non-uric acid calculi in the upper pole may be most amenable to observation.

Global analysis of differentially expressed genes during progression of calcium oxalate nephrolithiasis

The process of nephrolithiasis development is poorly understood at the molecular level. Here, we constructed a cDNA microarray from a rat kidney normalized cDNA library, and investigated the pattern of gene expression in rat kidneys from a calcium oxalate (CaOx) nephrolithiasis model. One hundred and seventy-three genes were found to be at least 2-fold regulated at one or more time points during progression of nephrolithiasis. RT-PCR and immunohistochemical analyses confirmed differential expression at both transcriptional and translational levels of genes identified by cDNA microarray screening. The differentially regulated genes were grouped into six clusters based on their expression profiles; the magnitude and the temporal patterns of gene expression identified known and novel molecular components involved in inflammation and matrix expansion in the CaOx nephrolithiasis kidney. This microarray study is the first report on gene expression programs underlying the process of nephrolithiasis.