28 novel mutations identified from 33 Chinese patients with cilia-related kidney disorders.

BACKGROUND: Cilia play an important role in cellular signaling pathways. Defective ciliary function causes a variety of disorders involve retina, skeleton, liver, kidney or others. Cilia-related kidney disorders are characterized by cystic renal disease, nephronophthisis and renal failure in general. METHODS: In this study, we collected 33 families clinically suspected of cilia-related kidney disorders. Capture-based next-generation sequencing (NGS) of 88 related genes, Sanger sequencing, pedigree analysis and functional study were performed to analyze their genetic cause. RESULTS: 40 mutations in PKD1, PKD2, PKHD1, DYNC2H1 and TMEM67 genes were identified from 27 of 33 affected families. 70% (28/40) of the mutations were first found in patients. We reported a very early-onset autosomal dominant polycystic kidney disease (ADPKD) family caused by a novel heterozygous PKD1 mutation; another fetus with DYNC2H1 compound heterozygous missense mutations showed mainly kidney dysplasia instead of skeletal abnormalities; and a novel PKD1 mutation, c.12445-3C > G, was confirmed to cause two wrong splicing modes. As for previously reported mutations, such as PKD1, c.6395 T > G (p.F2132C) and c.6868G > T (p.D2290Y), we had new and different findings. CONCLUSION: The findings provided new references for genotype-phenotype analyses and broadened the mutation spectrum of detected genes, which were significantly valuable for prenatal diagnosis and genetic counseling.

Generation of human induced pluripotent stem cells from peripheral blood mononuclear cells of a Senior-Loken syndrome patient.

Senior-Loken syndrome (SLS) is a rare disorder primarily associated with kidney and retinal dysfunction. We generated a human induced pluripotency stem cell (hiPSC) line, designated DKHi005-A, from peripheral blood mononuclear cells of a patient with SLS using a Sendai virus reprogramming method. We confirmed that DKHi005-A cells harbor the same mutation as the patient and show a normal karyotype. DKHi005-A also has pluripotency and the capacity for differentiation into the three germ layers. This cell line is registered and available at the National Stem Cell Bank, Korea National Institute of Health.

Angiotensinogen and interleukin 18 in serum and urine of children with kidney cysts.

BACKGROUND: The most common disease associated with the presence of kidney cysts in the population is autosomal dominant polycystic kidney disease (ADPKD), which finally leads to end-stage renal disease. METHOD: The study evaluated serum and urinary concentration of angiotensinogen (AGT) and interleukin 18 (IL-18) in a group of 39 children with renal cysts of different aetiology. RESULTS: Serum and urinary AGT concentration in children with renal cysts was higher compared to controls, regardless of the underlying background and gender. Serum IL-18 concentration was lower, in contrast, and the concentration of IL-18 in the urine did not differ between affected and healthy children. Negative correlation between urinary IL-18 concentration and systolic and mean arterial blood pressure was noted. CONCLUSIONS: Higher AGT levels in serum and urine in children with renal cysts may indicate the activation of the renin-angiotensin-aldosterone system, including its intrarenal part, even before the onset of hypertension. Lower serum concentration of IL-18 in children with kidney cysts may indicate the loss of the protective role of this cytokine with the occurrence of hypertension.

Hypomagnesaemia is absent in children with autosomal dominant polycystic kidney disease.

BACKGROUND: Hypomagnesaemia is present in 40-50% of children with autosomal dominant renal cysts and diabetes syndrome (RCAD). On the contrary, the prevalence of hypomagnesaemia in children with autosomal dominant polycystic kidney disease (ADPKD) has never been examined. We aimed to investigate whether hypomagnesaemia is present in children with polycystic kidney diseases. METHODS: Children with cystic kidney diseases were investigated in a cross-sectional study. Serum concentrations of magnesium (S-Mg) and fractional excretion of magnesium (FE-Mg) were tested. Fifty-four children with ADPKD ( n = 26), autosomal recessive polycystic kidney disease (ARPKD) ( n = 16) and RCAD ( n = 12) with median age of 11.2 (0.6-18.6) years were investigated. RESULTS: Hypomagnesaemia (S-Mg < 0.7 mmol/L) was detected in none of the children with ADPKD/ARPKD and in eight children (67%) with RCAD. Median S-Mg in children with ADPKD/ARPKD was significantly higher than in children with RCAD (0.89 vs. 0.65 mmol/L, P < 0.01). The FE-Mg was increased in 23% of patients with ADPKD/ARPKD (all had chronic kidney disease stages 2-4) and in 63% of patients with RCAD, where it significantly correlated with estimated glomerular filtration rate (r = -0.87, P < 0.01). CONCLUSIONS: Hypomagnesaemia is absent in children with ADPKD or ARPKD and could serve as a marker for differential diagnostics between ADPKD, ARPKD and RCAD in children with cystic kidney diseases of unknown origin where molecular genetic testing is lacking. However, while hypomagnesaemia, in the absence of diuretics, appears to rule out ADPKD and ARPKD, normomagnesaemia does not rule out RCAD at least in those aged <3 years.

New insights into the role of HNF-1ß in kidney (patho)physiology.

Hepatocyte nuclear factor-1ß (HNF-1ß) is an essential transcription factor that regulates the development and function of epithelia in the kidney, liver, pancreas, and genitourinary tract. Humans who carry HNF1B mutations develop heterogeneous renal abnormalities, including multicystic dysplastic kidneys, glomerulocystic kidney disease, renal agenesis, renal hypoplasia, and renal interstitial fibrosis. In the embryonic kidney, HNF-1ß is required for ureteric bud branching, initiation of nephrogenesis, and nephron segmentation. Ablation of mouse Hnf1b in nephron progenitors causes defective tubulogenesis, whereas later inactivation in elongating tubules leads to cyst formation due to downregulation of cystic disease genes, including Umod, Pkhd1, and Pkd2. In the adult kidney, HNF-1ß controls the expression of genes required for intrarenal metabolism and solute transport by tubular epithelial cells. Tubular abnormalities observed in HNF-1ß nephropathy include hyperuricemia with or without gout, hypokalemia, hypomagnesemia, and polyuria. Recent studies have identified novel post-transcriptional and post-translational regulatory mechanisms that control HNF-1ß expression and activity, including the miRNA cluster miR17 ∼ 92 and the interacting proteins PCBD1 and zyxin. Further understanding of the molecular mechanisms upstream and downstream of HNF-1ß may lead to the development of new therapeutic approaches in cystic kidney disease and other HNF1B-related renal diseases.

Renal cystic disease in the Fbn1C1039G/+ Marfan mouse is associated with enhanced aortic aneurysm formation.

Marfan syndrome (MFS) is a connective tissue disorder caused by mutations in the fibrillin-1 gene (FBN1), resulting in aortic aneurysm formation and dissections. Interestingly, variable aortopathy is observed even within MFS families with the same mutation. Thus, additional risk factors determine disease severity. Here, we describe a case of a 2-month-old Fbn1C1039G/+ MFS mouse with extreme aortic dilatation and increased vascular inflammation, when compared to MFS siblings, which coincided with unilateral renal cystic disease. In addition, this mouse presented with increased serum levels of creatinine, angiotensin-converting enzyme, corticosterone, macrophage chemoattractant protein-1, and interleukin-6, which may have contributed to the vascular pathology. Possibly, cystic kidney disease is associated with aneurysm progression in MFS patients. Therefore, we propose that close monitoring of the presence of renal cysts in MFS patients, during regular vascular imaging of the whole aorta trajectory, may provide insight in the frequency of cystic kidney disease and its potential as a novel indicator of aneurysm progression in MFS patients.

The relationship between simple renal cysts and glomerular filtration rate in the elderly.

PURPOSE: This cross-sectional study aimed to examine the association between the presence of simple renal cyst and glomerular filtration rate (GFR) in a group of elderly patients. METHODS: This study included 207 elderly subjects residing in a nursing home. All subjects underwent ultrasonography examination as well as serum urea and creatinine measurements. Creatinine clearance was calculated according to Cockroft-Gault formula. In addition, demographic data were recorded. RESULTS: Sixty-six subjects had simple renal cysts, and cysts were more frequent among male patients (43.1 vs. 28.2 %, p = 0.047). In addition, patients with renal cysts were slightly older and had a slightly lower GFR. On the other hand, patients with or without renal cysts did not differ with regard to renal sizes. In univariate analysis, reduced GFR was associated with older age (81.2 ± 5.9 vs. 75.7 ± 5.1 years, p < 0.001) and was more frequent among females (69.2 vs. 52.9 %, p = 0.034). In addition, lower BMI, presence of cyst, lower mean renal length, and lower mean renal thickness were associated with impaired GFR (p < 0.05 for all); however, number or bilaterality of the cysts were not linked with deterioration of GFR. Multivariate analysis identified only female gender (OR 2.4, 95 % CI 1.1-5.1, p = 0.030), a small BMI (<25; OR 6.2, 95 % CI 2.4-15.5, p < 0.001), and advanced age as independent predictors of low GFR. Each year increase in age results in OR 1.2 (95 % CI 1.1-1.3, p < 0.001). CONCLUSION: Presence of simple renal cyst does not seem to have an effect on the decline in GFR in elderly patients. Age-related increase in the incidence of renal cysts appears to occur in geriatric population.

Retrospective evaluation of ultrasound-indeterminate renal multilocular cystic masses by using neutrophil-lymphocyte ratio and computed tomography.

PURPOSE: To evaluate the clinical usefulness of neutrophil-lymphocyte ratio (NLR) in differentiating the ultrasound-indeterminate renal multilocular cystic masses (RMCM) in comparison with computed tomography (CT) and whether NLR has additional benefits to CT on sensitivity of detecting the malignant. MATERIALS AND METHODS: Overall, 93 patients who underwent normal ultrasound with a conclusion of indeterminate RMCM were examined by NLR and CT within 30 days before surgery or follow-up from March to September 2014 at PLA General Hospital and enrolled in this retrospective study. Logistic regression model was performed to find independent predictors for differentiating true nature of RMCM; differences in the validity parameters and diagnostic power of CT, NLR, and their combination were compared using McNemar tests and AUC model, respectively. RESULTS: The final diagnoses of the 93 patients consisted of 36 patients with benign complex cysts, 16 with multilocular cystic renal cell carcinoma, 9 with multilocular cystic nephroma, and 32 with clear cell renal cell carcinoma. Higher NLR were strongly associated with malignant masses. Multivariate logistic regression analysis revealed that NLR could be an independent predictor for differentiating true nature of these masses (OR = 3.617; 95% CI: 1.219-10.727; P = 0.020). For detecting the malignant masses, the sensitivity, specificity, and accuracy were 71.9%, 80.6%, and 75.3% for CT and 57.9%, 88.9%, and 69.9% for NLR under cutoff value of 2.31, respectively, whereas those of CT+NLR were 89.5%, 69.4%, and 81.7%. No significant difference was found between CT and NLR in sensitivity (P = 0.185), specificity (P = 0.549), and accuracy (P = 0.428). But the sensitivity of CT+NLR was significantly higher than those of CT (P = 0.002) and NLR (P<0.001), respectively; AUC model analysis indicated that CT+NLR got the largest area of 0.795 (P<0.001, 95% CI: 0.693-0.896) in comparison with those of CT (area = 0.795, P<0.001, 95% CI: 0.661-0.864) and NLR (area = 0.734, P<0.001, 95% CI: 0.631-0.836). CONCLUSIONS: Given that NLR, under cutoff value of 2.31, had no diagnostic difference with CT in evaluating the ultrasound-indeterminate RMCM. However, combination of CT and NLR could increase the sensitivity of detecting malignant masses and acquire the best diagnostic power. Prospectively larger cohort and multicenter studies are still necessary.

Simple renal cyst and renal dysfunction: A pilot study using dimercaptosuccinic acid renal Scan.

AIM: Little is known about the association between renal cyst and renal dysfunction. We evaluated the deterioration of renal function in patients with unilateral, large, simple renal cysts. METHODS: Fifty patients with unilateral, simple renal cysts measuring ≥ 4 cm (cyst group) and 50 kidney donors (control group) were enrolled. Dimercaptosuccinic acid (DMSA) renal scans were performed to calculate split renal function. The differences between split renal function were calculated and compared. Clinical factors affecting decreased renal function in the cyst group were assessed. RESULTS: The mean age of the patients in the cyst group was higher than the control group (59.1 vs 39.2 years; P = 0.001). Patients with renal cysts tended to be diagnosed with hypertension (P = 0.001), However, the two groups did not significantly differ in terms of the other characteristics. The median cyst size was 7.2 cm (range, 4.5-14.2), and 31 of the 50 patients (60.2%) in the cyst group demonstrated decreased renal function in the cystic kidney units (median: 5.8%; range, 0.2-33). Although there were no differences in split renal function (50.1% vs 49.9%; P = 0.629) in the control group, the relative renal function of the cystic kidney units were significantly lower than the contralateral kidney units in the cyst group (48.3% vs 51.7%; P = 0.001). The decrease in relative renal function (>8%) in the cystic kidney units was associated with a higher serum uric acid levels and higher RENAL complexity (P = 0.035 and P = 0.007, respectively). CONCLUSION: A significant proportion of unilateral, large, simple renal cysts are associated with decreased relative renal function on DMSA renal scans.

Renalase: Another puzzle piece between hypertension and simple renal cysts?

BACKGROUND AND AIM: Since renalase is mostly expressed in kidney tubules, simple renal cyst (SRC) originates from the kidney tubules, and both conditions are related to hypertension, it may be possible that SRC is associated with increased renalase levels. Therefore, in the current study we aimed to confirm the relation between renalase and epinephrine levels, the association between SRC and renalase levels and the association between renalase, blood pressure levels and endothelial dysfunction. MATERIALS AND METHODS: We made a cross-sectional study including 75 patients with SRC, and 51 controls were included to the study. Flow-mediated dilatation (FMD) was assessed, and serum renalase and epinephrine levels were determined. RESULTS: Patient with SRC had lower renalase, higher epinephrine and lower FMD levels when compared to patients without SRC (p < 0.05). Log renalase was correlated with log epinephrine (r = -0.302, p = 0.001) and log FMD (r = 0.642, p < 0.0001). There was no correlation between renalase and urine albumin/creatinine ratio and glomerular filtration rate. In univariate analysis, age, glomerular filtration rate, renalase and FMD were associated with the presence of SRC. Multivariate regression analysis of factors which are statistically significant in univariate analysis showed that age and renalase was associated with the presence of SRC. CONCLUSION: We have demonstrated that renalase levels were associated with the presence of SRC and endothelial dysfunction. Further research is necessary to highlight underlying mechanisms.

Ten-year treatment outcomes including blood cell count disturbances in patients with simple renal cysts.

BACKGROUND: The simple renal cyst is the most common benign kidney disease. It may cause pain and hypertension, especially if significantly enlarged. As in polycystic kidney disease, blood cell count disturbances are frequently observed in simple renal cysts. The aim of our study was to assess such disturbances, changes in blood pressure, and complication rate in our patients undergoing surgery due to simple renal cyst in the last 10 years. MATERIAL AND METHODS: 210 patients with simple renal cysts were underwent surgery between 2002 and 2012. Two different kinds of operation were conducted: aspiration of cyst fluid with injection of sclerosing agent, and laparoscopic/retroperitoneoscopic decortications of the cyst wall. A control group comprised 134 patients with benign prostate hyperplasia. The following data were obtained: cyst burden, hematocrit, hemoglobin, red blood cells, thrombocytes, occurrence of pain, and blood pressure before and after the operation. Complications were collected and presented in Clavien score. RESULTS: Hematocrit, hemoglobin, and red blood cells were significantly increased in the experimental group. A positive correlation was observed between cyst burden and the parameters mentioned above. Of 91 patients with hypertension, 56 (61.7%) had blood pressure reduction after the operation. Treatment relieved the loin pain in 132 (88%) patients. Complications occurred in 15 (7.4%) patients. CONCLUSIONS: Patients with simple renal cysts have high values of red blood cells, hematocrit, and hemoglobin. Treatment decreases blood pressure in patients with hypertension. Complications after treatment are rare and mild.

Multiple and large simple renal cysts are associated with prehypertension and hypertension.

Although simple renal cysts are thought to be related to hypertension, no reports have examined the relationship between simple renal cysts and prehypertension. Here, we evaluated the effects of simple renal cysts on prehypertension and hypertension and the role of serum renin levels in the cyst-related prehypertension/hypertension in adults. A total of 14,995 patients were enrolled and divided into normotension, prehypertension, and hypertension groups. Simple renal cysts were classified into different categories based on number (1 vs. ≥ 2 cm) and size (<2 vs. ≥ 2 cm). In multivariate analysis, simple renal cysts were independently related to prehypertension/hypertension. Two or more simple renal cysts or cyst of ≥ 2 cm were independently associated with prehypertension/hypertension. However, the association between cyst of ≥ 2 cm and prehypertension/hypertension disappeared after further adjusting for serum renin level in an exposure-matched subgroup analysis. Thus, the presence of two or more simple renal cysts and cyst of ≥ 2 cm were the important determinants of prehypertension and hypertension in adults. One possible mechanism of cyst-related prehypertension/hypertension may be related to an increased serum renin level. We recommend close monitoring of blood pressure routinely among patients with two or more simple renal cysts.

NGAL as an early biomarker of kidney disease in Joubert syndrome: three brothers compared.

Joubert syndrome (JBTS) is a rare autosomal recessive disorder with an underestimated prevalence due to lack of recognition of clinical signs or failure to diagnose this pathology. JBTS is clinically heterogeneous, and it is characterized by a multiple organ involvement predominantly due to the requirement for Joubert gene function in several tissues. Renal disease affects approximately 30% of patients with JBTS, presenting itself in most cases as nephronophthisis (NPHP), a structural tubulo-interstitial disorder characterized by thickened basal membrane of the tubular epithelium and progressive interstitial fibrosis, associated with cysts at the cortico-medullary junction. We propose three cases concerning three patients with JBTS having different years of illness and degrees of renal impairment, evaluating the parameters of renal function at the time of genetic diagnosis and seen after a follow-up of 7 years. We measured neutrophil gelatinase-associated lipocalin (NGAL), considered as an excellent predictor of kidney injury, to evaluate whether this biomarker might be an early biomarker for JBTS-related kidney disease. NGAL was high in all three cases, but with different levels, indicating a tubular suffering typical of this syndrome, with dissimilar severity in the analyzed subjects. NGAL could represent an early indicator of renal damage useful to start an intensive nephrologic follow-up.

Brief report: Why did two patients who type for HLA-B13 have antibodies that react with all Bw4 antigens except HLA-B13?

Two transplant candidates sensitized during pregnancy by a B*44:02 mismatch showed antibodies that reacted with an epitope defined by the 145R+82LR eplet pair shared by all Bw4 antigens in single allele Luminex panels except B13. Both eplets are on one or more alleles of the antibody producer and according to HLAMatchmaker, they are considered intralocus and interlocus matches which should not induce antibodies. The recently developed nonself-self paradigm for HLA epitope immunogenicity has offered a ready explanation why the pair of self-145R and self-82LR eplets on B*44:02 induced specific antibodies. This finding is consistent with the concept that alloantibody responses originate from B-cells with self-HLA immunoglobulin receptors.

Phenotype and outcome in hereditary tubulointerstitial nephritis secondary to UMOD mutations.

BACKGROUND: UMOD mutations cause familial juvenile hyperuricemic nephropathy (FJHN) and medullary cystic kidney disease (MCKD), although these phenotypes are nonspecific. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We reviewed cases of UMOD mutations diagnosed in the genetic laboratories of Necker Hospital (Paris, France) and of Université Catholique de Louvain (Brussels, Belgium). We also analyzed patients with MCKD/FJHN but no UMOD mutation. To determine thresholds for hyperuricemia and uric-acid excretion fraction (UAEF) according to GFR, these parameters were analyzed in 1097 patients with various renal diseases and renal function levels. RESULTS: Thirty-seven distinct UMOD mutations were found in 109 patients from 45 families, all in exon 4 or 5 except for three novel mutations in exon 8. Median renal survival was 54 years. The type of mutation had a modest effect on renal survival, and intrafamilial variability was high. Detailed data available in 70 patients showed renal cysts in 24 (34.3%) of nonspecific localization in most patients. Uricemia was >75th percentile in 31 (71.4%) of 42 patients not under dialysis or allopurinol therapy. UAEF (n = 27) was <75th percentile in 70.4%. Among 136 probands with MCKD/FJHN phenotype, UMOD mutation was found in 24 (17.8%). Phenotype was not accurately predictive of UMOD mutation. Six probands had HNF1B mutations. CONCLUSIONS: Hyperuricemia disproportionate to renal function represents the hallmark of renal disease caused by UMOD mutation. Renal survival is highly variable in patients with UMOD mutation. Our data also add novel insights into the interpretation of uricemia and UAEF in patients with chronic kidney diseases.

Placebo-controlled, double-blind study of the non-purine-selective xanthine oxidase inhibitor Febuxostat (TMX-67) in patients with hyperuricemia including those with gout in Japan: phase 3 clinical study.

BACKGROUND: : Allopurinol has been widely used for treatment of hyperuricemia, however, it may be associated with various adverse effects. Febuxostat has been identified as a potentially safe and efficacious alternative. OBJECTIVES: : A multicenter study with randomized, placebo-controlled, double-blind, parallel-group comparison was carried out to evaluate the efficacy and safety of febuxostat in 103 patients with hyperuricemia (including patients with gout) in Japan. METHODS: : Subjects were treated with febuxostat (20 or 40 mg/d) or a placebo for 8 weeks. The variables evaluated were the percentage of patients achieving serum uric acid levels 6.0 mg/dL or less and the percent change in serum uric acid levels after 8 weeks. RESULTS: : The percentage of patients achieving serum uric acid levels 6.0 mg/dL or less after 8 weeks was 91.2% in the febuxostat 40-mg/d group, 45.7% in the 20-mg/d group, and 0.0% in the placebo group. The percent changes in serum uric acid levels after 8 weeks were -44.9% in the febuxostat 40-mg/d group, -28.9% in the 20-mg/d group, and -0.6% to -0.5% in the placebo group. No severe or medically significant adverse reaction attributable to febuxostat was noted, and there was no event that could pose a clinical problem. The efficacy did not differ depending on the presence/absence of gout history. CONCLUSIONS: : These results suggest that febuxostat (20 or 40 mg/d) is useful as a new means of treating hyperuricemia and is capable of reducing serum uric acid levels to 6.0 mg/dL or less (goal of treatment) with high safety regardless of the presence/absence of gout history.

Hypokalemic paralysis associated with cystic disease of the kidney: case report.

BACKGROUND: Severe hypokalemia is known to cause muscle paralysis, and renal tubular acidosis is a recognized cause. Cystic disease of the kidney is associated with severe hypokalemia. CASE PRESENTATION: We report a 33-year-old male patient who presented with generalized limb weakness caused by severe hypokalemia due to renal tubular acidosis, who was found to have renal medullary cysts. CONCLUSION: The association of cystic renal disease with hypokalemia, and the possible pathophysiological basis of the development of renal cysts in patients with severe hypokalemia, are discussed.

Relationship between levels of serum creatinine and perirenal hyperintensity on heavily T2-weighted MR images.

OBJECTIVE: To determine the frequency of perirenal hyperintensity on heavily T2-weighted images and to evaluate its relationship with serum creatinine levels. SUBJECTS AND METHODS: Axial and coronal single-shot fast spin-echo images which have been originally obtained for MR cholangiopancreatography in 150 subjects were examined by two observers individually for the presence of perirenal hyperintensity. The morphologic properties of perirenal hyperintensity (peripheral rim-like, discontinuous, polar) were recorded. Chi square test was used to test whether the frequencies of bilateral perirenal hyperintensity differ significantly in subjects with high serum creatinine levels and those with normal creatinine levels. This test was also used to compare the frequencies of perirenal hyperintensity in patients with and without renal cysts and in patients with and without corticomedullary differentiation. A p value of less than 0.05 was considered to be statistically significant. RESULTS: The perirenal hyperintensity was identified in 40 of 150 cases (26.6%) on heavily T2-weighted image. Serum creatinine levels were high in 18 of 150 cases (12%). The perirenal hyperintensity was present in 11 of 18 subjects (61%) with high serum creatinine levels and 26 of 132 subjects (19.7%) with normal creatinine levels. The difference of rates in two groups was statistically significant. Odds ratio was 6407 (95% confidence interval 2264 -18,129) . The frequency of perirenal hyperintensity was also significantly higher in subjects with renal cyst or cysts in whom serum creatinine levels were normal (p<0.05) (37.5% vs. 11.8%). CONCLUSION: Perirenal hyperintensities are more frequent in patients with high serum creatinine levels. They are also more common in patients with simple renal cysts.

[Are simple renal cysts another manifestation of prelithiasis in infancy?]. / ¿Los quistes renales simples son otra forma de manifestación de prelitiasis en la infancia?

Simple renal cysts are uncommon lesions in paediatric patients. In the absence of hypokalaemia or an increase in the production of NH+, the cause of simple renal cysts is unknown. Hepler, in 1930, suggested that they may be caused by a tubular obstruction. We prospectively studied the presence of hypercalciuria or hypocitraturia as well as the family history of urolithiasis in a group of children diagnosed sonographically with simple renal cysts. The average age of the 22 patients (12M, 10F) was 6.04 +/- 2.9 years at the time of diagnosis. The ultrasound examination had been requested due to urinary tract infection, abdominal pain, haematuria or other disorders. The cysts were slightly more frequent on the left side (54.5%). All were located in the upper kidney pole. 14 patients were found to have hypercalciuria and/or hypocitraturia (hypercalciuria n = 11, 50%). Thirteen families had history of renal stones. The metabolic abnormalities associated with calculi in children and/or family history of stones were present in 19 families (86.3%). Our hypothesis is that both entities, renal cysts, and genetic predisposition to kidney stones, are related.

Utility of cystatin C to monitor renal function in Duchenne muscular dystrophy.

Creatinine as a marker of renal function has limited value in Duchenne muscular dystrophy (DMD) because of reduced muscle mass. Alternative methods of assessing renal function are sorely needed. Cystatin C, a nonglycosylated protein unaffected by muscle mass, is potentially an ideal biomarker of nephrotoxicity for this population but requires validation. In all, 75 subjects were recruited: 35 DMD (mean age 10.8 +/- 5.4 years, corticosteroids n = 19, ambulatory n = 26), 29 healthy controls, 10 with renal disease, and one DMD with renal failure. Cystatin C levels in DMD were normal irrespective of age, ambulation, or corticosteroid treatment. Serum cystatin C was 0.67 +/- 0.11 mg/l compared to normal controls 0.69 +/- 0.09. mg/l. In these same individuals serum creatinine was severely reduced (0.27 +/- 0.12 mg/dl) versus normals (0.75 +/- 0.15 mg/dl, P < 0.01). In one DMD subject in renal failure, cystatin C was elevated. This study demonstrates the potential value of cystatin C as a biomarker for monitoring renal function in DMD. Its applicability extends to other neuromuscular diseases.