Comprehensive evaluation of patients with primary hyperoxaluria type 1: A nationwide study.

BACKGROUND: Primary hyperoxaluria type 1 (PH1) is characterized by increased endogenous oxalate production and deposition as calcium oxalate crystals. The main manifestations are nephrocalcinosis/nephrolithiasis, causing impaired kidney function. We aimed to evaluate the clinical characteristics and overall outcomes of paediatric PH1 patients in Turkey. METHODS: This is a nationwide, multicentre, retrospective study evaluating all available paediatric PH1 patients from 15 different paediatric nephrology centres in Turkey. Detailed patient data was collected which included demographic, clinical and laboratory features. Patients were classified according to their age and characteristics at presentation: patients presenting in the first year of life with nephrocalcinosis/nephrolithiasis (infantile oxalosis, Group 1), cases with recurrent nephrolithiasis diagnosed during childhood (childhood-onset PH1, Group 2), and asymptomatic children diagnosed with family screening (Group 3). RESULTS: Forty-eight patients had a mutation consistent with PH1. The most common mutation was c.971_972delTG (25%). Infantile oxalosis patients had more advanced chronic kidney disease (CKD) or kidney failure necessitating dialysis (76.9% vs. 45.5%). These patients had much worse clinical course and mortality rates seemed to be higher (23.1% vs. 13.6%). Patients with fatal outcomes were the ones with significant comorbidities, especially with cardiovascular involvement. Patients in Group 3 were followed with better outcomes, with no kidney failure or mortality. CONCLUSION: PH1 is not an isolated kidney disease but a systemic disease. Family screening helps to preserve kidney function and prevent systemic complications. Despite all efforts made with traditional treatment methods including transplantation, our results show devastating outcomes or mortality.

Comparison of infants and children with urolithiasis: a large case series.

We evaluated the demographic features, etiologic risk factors, treatment strategies, and outcome of the infants and children with urolithiasis (UL). A retrospective multicenter study was conducted including 23 Pediatric Nephrology centers in Turkey. The medical records of 2513 children with UL were reviewed. One thousand, three hundred and four boys and 1209 girls (1.1:1) were reported. The mean age at diagnosis was 39.5 ± 35 months (0.4-231 months), and 1262 patients (50.2%) were in the first year of life (infants). Most of the cases with infantile UL were diagnosed incidentally. Microlithiasis (< 3 mm) was found in 794 patients (31.6%), and 64.5% of the patients with microlithiasis were infants. Stones were located in the pelvis-calyces in 63.2% (n: 1530) of the cases. The most common stone type was calcium oxalate (64.6%). Hypocitraturia was the most common metabolic risk factor (MRF) in children older than 12 months, but in infancy, hypercalciuria was more common. Fifty-five percent of the patients had received at least one medical treatment, mostly potassium citrate. At the end of a year's follow-up, most of the patients with microlithiasis (85%) showed spontaneous remission. The rate of spontaneous stone resolution in infants was higher than in children. Spontaneous remission rate was higher in cases with MRF ( - ) stones than in MRF ( +) stones. However, remission rate with medical treatment was higher in cases with MRF ( +) stones. This study represents the results of a large series of infants and children with UL and showed that there are several differences such as underlying metabolic and anatomic abnormalities, clinical course, and stone remission rates between infants and children with urinary stone disease.

Evaluation of subclinical cardiovascular risk and cardiac function in children with vesicoureteral reflux: a prospective study.

BACKGROUND: Vesicoureteral reflux is a prominent congenital anomaly of the kidney and the urinary tract. Further, renal scarring is known to be related to chronic inflammation. However, there have been limited studies to date regarding the cardiovascular consequences of vesicoureteral reflux. OBJECTIVE: The aim of this study is to evaluate the possible subclinical atherosclerosis and cardiovascular complications in children with vesicoureteral reflux. METHODS: Patients with vesicoureteral reflux and age matched healthy controls were prospectively included in this case-control study. Patients were divided into two groups concerning renal scarring status. To assess cardiac functions, carotid artery intima media, epicardial adipose tissue, and periaortic adipose tissue thicknesses were evaluated. RESULTS: There were 50 patients with vesicoureteral reflux; 26 patients without renal scarring and 24 patients with renal scarring, as well as 40 healthy controls. Myocardial performance indexes (Tei indexes) measured by tissue Doppler echocardiography from septum and left ventricle were significantly increased in study group (for all, p < 0.001). Also, intima media, epicardial adipose tissue, and periaortic adipose tissue thicknesses of the study groups were significantly higher than the control group (for all, p < 0.001). However, no statistical difference was observed between renal scarring (-) and renal scarring (+) groups. CONCLUSIONS: Results of our study showed early deterioration of cardiac systolic and diastolic functions in children with vesicoureteral reflux regardless of renal scarring. Also, diagnosis of vesicoureteral reflux is an important risk factor for subclinical atherosclerosis, independent of renal scarring, which should be considered in the follow-up of these patients.

The association between the congenital heart diseases and congenital anomalies of the kidney and the urinary tract in nonsyndromic children.

Several congenital heart diseases (CHD) are present in children with congenital anomalies of the kidney and the urinary tract (CAKUT) in syndromic or nonsyndromic patterns. The purpose of this study was to identify nonsyndromic children with CAKUT who required echocardiographic evaluation and to find the prevalence of CHD in these patients. Retrospective chart review of nonsyndromic patients with CAKUT between 2012 and 2018 was conducted. Types of congenital anomalies of the kidney and urinary tract and echocardiogram reports of the patients, age, gender, prematurity, prenatal diagnosis of CAKUT, and family history were noted. Among 806 children with CAKUT, 135 patients underwent transthoracic echocardiographic evaluation and CHD was detected in 91 (11.2%). The most common type of CHD was secundum type atrial septal defect that was found in 73 (80.2%) patients. On the other hand, the most frequent types of congenital anomalies of the kidney and the urinary tract were isolated hydronephrosis and primary vesicoureteral reflux (61.4% and 12.8%, respectively). Our results showed that 75.8% of the patients with congenital heart diseases had isolated hydronephrosis. Finally, only 18 (2.2%) cases out of 806 patients that were evaluated via transthoracic echocardiography due to the clinical findings and family history had a CHD that required close (<6 months) follow-up. Congenital heart diseases that required close follow-up are rarely observed in nonsyndromic patients with CAKUT. Therefore, we suggest echocardiography should be performed in cases of clinical suspicion and family history rather than routinely in this patient group.

A nationwide retrospective study in Turkish children with nephrocalcinosis.

BACKGROUND: Nephrocalcinosis (NC) is defined as calcium deposition in the kidney parenchyma and tubules. This study aims to determine the etiology, risk factors, and follow-up results of patients with NC in Turkey. METHODS: Patients diagnosed with NC in the pediatric nephrology Department Units of 19 centers from all geographical regions of Turkey over a 10-year period (2010-2019) were included in the study. The medical records from the centers were reviewed and demographic data, admission complaints, medical history, systemic and genetic disorders, risk factors for NC, treatment details, and presence of NC after one-year follow-up, were recorded retrospectively. RESULTS: The study sample included 195 patients (88 females, 107 males). The mean age at diagnosis was 39.44 ± 47.25 (0.5-208) months; 82/190 patients (43.2%) were diagnosed incidentally; 46/195 patients (23.6%) had an underlying disease; idiopathic hypercalciuria was detected in 75/195 (38.4%) patients. The most common systemic diseases were distal renal tubular acidosis in 11/46 patients (23.9%), primary hyperoxaluria in 9/46 patients (19.6%) and Bartter syndrome in 7/46 patients (15.3%). After one year of follow-up, NC resolved in 56/159 patients (35.2%) and they all did not have an underlying systemic disease. DISCUSSION: The most common presentation of NC was incidental. Distal renal tubular acidosis and primary hyperoxaluria were the main systemic diseases leading to NC, while hypercalciuria was the most common metabolic risk factor. Nephrocalcinosis was found to remain in most of the patients at a one-year follow-up. It may resolve particularly in patients with no underlying systemic disease.

Incidence of primary vesicoureteral reflux in patients with febrile convulsions.

The aim of this study is to evaluate the incidence of vesicoureteral reflux (VUR) in patients with febrile convulsion (FC). For this, patients that were diagnosed with FC in 2018 were retrospectively reviewed. Those with epilepsy, motor/mental retardation, or spina bifida were excluded. Mid-stream urine samples were collected in children who were toilet trained while sterile bags were used in the smaller. Urinary tract infection (UTI) was defined as ˃ 5 leucocytes/HPF in urinalysis and a subsequent positive urine culture (≥ 10.000 CFU/ml). Children with UTI were further investigated via voiding cystourethrogram (VCUG) and dimercaptosuccinic acid (DMSA) scintigraphy for VUR. Urinalysis was present in 79 among a total of 181 patients (43.6%). Forty-five of the patients were male (57%). Mean age was 2.6 ± 1.4 years. UTI was diagnosed in 6 (7.6%) patients (5 females, 1 male). Three of the girls had recurrent febrile UTI and subsequently, VUR was diagnosed in two of them. VUR is found in 2.5% of the FC cases with urine sampling. Urinalysis should not be ignored in patients with FC as it may lead to diagnosis of VUR.

A rare congenital fusion anomaly of the urinary tract: Pancake kidney.

Pancake kidney is a rare subtype of cross fused renal ectopia. Fusion of both upper and lower poles of the kidney in pelvis results in a disc or cake shaped kidney appearence. In this report, we are presenting two cases (a 3-month-old male and a 3-year-old girl) with different presentations and their follow-up results. Usually, renal fusion anomalies do not pose a risk for deterioration of renal function. With this fact kept in mind, cases should be managed individually. Additionally, magnetic resonance imaging should be the preferred modality in which further evaluation is required since it can give both functional and anatomical detail with no radiation exposure.

Is voiding cystourethrography necessary for evaluating unilateral ectopic pelvic kidney?

OBJECTIVE: The aim of this study is to evaluate if voiding cystourethrography (VCUG) is necessary for the evaluation of unilateral ectopic pelvic kidney (UEPK) in order to identify vesicoureteral reflux (VUR). MATERIAL AND METHODS: Files of the patients who had been followed-up for ectopic pelvic kidney in two pediatric nephrology clinics between August 2011 and December 2017 were retrospectively reviewed. Other anomalies, such as crossed, fused, and bilateral pelvic ectopia were excluded. Preliminary diagnoses were made via urinary ultrasonography while dimercaptosuccinic acid scintigraphy was carried out to confirm the diagnoses. Differential renal function and presence of renal scars was checked. VCUG results were obtained and those patients that showed VUR were noted. RESULTS: A total of 72 patients were included in the study (41 males and 31 females). The median patient age was 4.1 years (range: 2 months-14.5 years). Hydronephrosis was present in only 4 patients (5.6%), where 1 one of those was on the contralateral side. UEPKs contributed to the mean 37.9±7.8% of total renal function and 15% of these patients had renal scars (expressed as a global reduction in function, not as patchy scars). VCUG was obtained in 42 patients and VUR was present in only 1 patient (2.4%). The median follow-up period was 16.5 months (range: 3-92 months). CONCLUSION: The results of our study indicated that hydronephrosis and VUR are not common in UEPKs. Therefore, routine VCUG should be avoided in the evaluation of UEPK in order to protect patients from unnecessary radiation exposure and an increased risk of urinary tract infections.

Follow-up results of patients with ADCK4 mutations and the efficacy of CoQ10 treatment.

BACKGROUND: ADCK4-related glomerulopathy is an important differential diagnosis in adolescents with steroid-resistant nephrotic syndrome (SRNS) and/or chronic kidney disease (CKD) of unknown origin. We screened adolescent patients to determine the frequency of ADCK4 mutation and the efficacy of early CoQ10 administration. METHODS: A total of 146 index patients aged 10-18 years, with newly diagnosed non-nephrotic proteinuria, nephrotic syndrome, or chronic renal failure and end-stage kidney disease (ESKD) of unknown etiology were screened for ADCK4 mutation. RESULTS: Twenty-eight individuals with bi-allelic mutation from 11 families were identified. Median age at diagnosis was 12.4 (interquartile range [IQR] 8.04-19.7) years. Upon first admission, all patients had albuminuria and 18 had CKD (6 ESKD). Eight were diagnosed either through the screening of family members following index case identification or during genetic investigation of proteinuria in an individual with a history of a transplanted sibling. Median age of these 8 patients was 21.5 (range 4.4-39) years. CoQ10 supplementation was administered following genetic diagnosis. Median estimated glomerular filtration rate (eGFR) just before CoQ10 administration was 140 (IQR 117-155) ml/min/1.73m2, proteinuria was 1,008 (IQR 281-1,567) mg/m2/day. After a median follow-up of 11.5 (range 4-21) months following CoQ10 administration, proteinuria was significantly decreased (median 363 [IQR 175-561] mg/m2/day, P=0.025), whereas eGFR was preserved (median 137 [IQR 113-158] ml/min/1.73m2, P=0.61). CONCLUSIONS: ADCK4 mutations are one of the most common causes of adolescent-onset albuminuria and/or CKD of unknown etiology in Turkey. CoQ10 supplementation appears efficacious at reducing proteinuria, and may thereby be renoprotective.

Do JJ Stents Increase the Effectiveness of Extracorporeal Shock Wave Lithotripsy for Pediatric Renal Stones?

PURPOSE: We aimed to evaluate the effects of preoperative urinary catheterization in nephrolithiasis treatment with extracorporeal shock wave lithotripsy (SWL). METHODS: Patients admitted to the Department of Pediatric Surgery for renal stones between June 2012 and June 2014 were evaluated retrospectively. Patients were divided into 2 groups based on JJ stent placements. Group 1 did not receive JJ stents, while group 2 did. The recorded demographic data for each group included age, gender, stone size, location, sessions, and complications. The Elmed Complit ESWL system was used with 11-13 kV, and 1,000-1,200 shots in patients 2-4 years of age, and 11-14 kV, and 1,000-1,500 shots for patients over 4 years. RESULTS: In group 1, 18 sessions of SWL were performed on 8 female and 2 male children with a mean age of 4.5 (range 2-12) years and stone diameter of 9 (range 7-15) mm. The locations of the renal stones were in the upper pole in 1 patient, 7 in the lower pole, and 2 in the pelvis renalis. Postoperatively, 1 patient had hematuria, 2 had dysuria, and one had a stone in the external urethral meatus. Eighty percent of patients were stone free; there were no fragmentations in 2 patients, and 1 patient discontinued treatment. In group 2, 15 SWL sessions were performed on 5 female and 5 male children aged 4 (range 3-5) and the stone diameter was 9 (range 7-16) mm. The locations of the renal stones were in the upper pole in 6 patients, in the lower pole in 3 patients, and in the ureteropelvic junction in one patient. JJ stents were placed in all patients preoperatively. Postoperatively, 3 patients had hematuria and one had dysuria. At the end of the study, all of the patients were stone free. Statistically, there were no differences in age, gender, stone size, location, and the number of sessions. CONCLUSIONS: Our results indicate that SWL without preoperative ureteral stenting is an effective and safe procedure that can be carried out in the pediatric population. Preoperative JJ stenting is unnecessary in patients, especially in those with smaller stone diameters.

Pediatric urolithiasis: metabolic risk factors and follow-up results in a Turkish region with endemic stone disease.

The goal of this study was to investigate the metabolic etiology, clinical findings and medical treatment of children with urolithiasis in an endemic region of Turkey. We retrospectively analyzed the medical records of 742 (437 males, 305 females) children with urolithiasis. Physical examination results, serum biochemistry and urine metabolic evaluation, including urinary citrate, oxalate, calcium, uric acid, cystine and magnesium levels were recorded. We obtained follow-up records in 316 patients to evaluate the association between stone recurrence and metabolic risk factors. The mean age at diagnosis was 2.6 ± 3.4 (0.1-17.0) years. Male-to-female ratio was 1.4:1. A family history of stone disease was found in 76.5 % of patients and 41 % of parents had consanguineous marriage. The most common presenting symptoms were urinary tract infection (UTI, 23.9 %) and hematuria (23.6 %). Metabolic abnormalities were found in 588 (79.2 %) patients, including hypercalciuria in 31.5 %, hypocitraturia in 24.2 %, hyperoxaluria in 11.4 %, hyperuricosuria in 9.1 %, hypomagnesuria in 3.9 %, and cystinuria in 3.1 % of patients. The frequency of hyperoxaluria and hypocitraturia were significantly higher in patients with new stone formation. Follow-up records of 316 (42.6 %) patients (192 males, 124 females) were available. Urolithiasis was shown in 135 (42.7 %) of the patients on control ultrasonography, and 61.5 % of these patients had a stone size ≤ 3 mm. Hyperoxaluria and cystinuria were significantly higher in patients with stone persistence. The main goal of management for children with urolithiasis should be identification of risk factors.

An unusual association between familial mediterranean fever and IgM nephropathy.

OBJECTIVE: To report a case with the diagnosis of IgM nephropathy and familial Mediterranean fever (FMF). CLINICAL PRESENTATION AND INTERVENTION: A 9-year-old boy was admitted to our hospital with recurrent abdominal pain since the age of 4 years. Laboratory investigations revealed a sedimentation rate of 88 mm/h, C-reactive protein: 83.2 mg/l (0-10 mg/l), white blood cell count: 12,700/mm(3), fibrinogen: 622 mg/dl (200-400 mg/dl) and serum amyloid A: 186 mg/l (0-5.8 mg/l). Urinalysis revealed +2 proteinuria. A 24-hour urinary protein excretion was 12 mg/m(2)/h. M694V homozygous mutation was identified in exon 10. Percutaneous renal biopsy showed mesangial cell proliferation and increased mesangial matrix in the glomeruli, without amyloid accumulation. Immunofluorescence study showed IgM (+1) and C1q (+1) deposits. Treatment with 1 mg/day colchicine was started. Six weeks later, proteinuria had disappeared and the patient was asymptomatic. CONCLUSION: This case illustrates the unusual association of FMF with non-amyloid glomerulopathy. Glomerular diseases such as IgM nephropathy may be seen as a manifestation of FMF.

Familial hypomagnesemia with hypercalciuria and nephrocalcinosis: report of three Turkish siblings.

Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC), an autosomal recessive renal tubular disorder is characterized by the impaired tubular reabsorption of magnesium and calcium in the thick ascending limb of the loop of Henle. This disease is caused by mutations in the claudin-16 gene (CLDN16), which encodes the tight junction protein, claudin-16. Claudin-16 belongs to the claudin family and regulates the paracellular transport of magnesium and calcium. Here, we report on three Turkish siblings with typical clinical features of FHHNC in association with the homozygous mutation Leu151Phe.

Henoch Schonlein purpura in childhood: clinical analysis of 254 cases over a 3-year period.

We aimed to evaluate the patients who were diagnosed as Henoch Schonlein purpura (HSP) for disease characteristics and prognosis of those with joint, gastrointestinal (GI), and renal involvement. Two hundred and fifty-four children who were followed up with the diagnosis of HSP in the Pediatric Nephrology Clinics of Meram Medical Faculty of Selcuk University and Medical Faculty of Gazi University between January 2003 and June 2006 were retrospectively evaluated. The clinical follow-up and treatment regimens of patients in whom renal biopsy was performed were evaluated in detail. The study group consisted of 254 children, 147 boys (57.8%) and 107 girls (42.2%), and the ratio of boys to girls was 1.37. The percentages of skin, joint, GI, and renal manifestations were 100%, 66%, 56%, and 30%, respectively. Eight patients had intussusception. Five of them recovered with steroid treatment only while three patients were operated on. Sixty-four patients (44%) with GI involvement had severe disease and were successfully treated with steroids. Renal biopsy was performed in 26 patients. Among those 26 patients, two of them recovered spontaneously within 3 and 4 weeks. Ten patients improved with only steroid treatment while 12 patients recovered with steroid and cyclophosphamide treatment. Two patients were resistant to steroid and cyclophosphamide treatment and were treated with cyclosporine A. We believe that steroid therapy given to the HSP patients with GI manifestations might be helpful to prevent probable complications such as GI bleeding and intussusception. In addition, combined therapy with steroid and cyclophosphamide can usually be an appropriate treatment for patients with nephrotic proteinuria.

The evaluation of carotid intima-media thickness in children with familial Mediterranean fever.

The aim is to investigate whether pediatric familial Mediterranean fever (FMF) patients have an increased risk of premature atherosclerosis and to determine the possible strength of association between atherosclerosis and Mediterranean fever (MEFV) gene mutation gene type. Demographic characteristics and MEFV mutations were defined in 49 children diagnosed with FMF (26 female, 23 male; mean age, 10.71 +/- 3.69 years). Twenty-six age-, sex-, and body-mass-index-matched healthy children constituted the control group. We evaluated the blood counts and acute-phase proteins during attack-free periods. Mean C-reactive protein (CRP), serum amyloid-A (SAA), homocysteine (Hcy), lipoprotein-a (Lp-a), and common carotid artery intima-media thickness (CCA-IMT) were 10.75 +/- 15.29 vs 4.03 +/- 1.20, 23.22 +/- 41.94 vs 3.53 +/- 1.04, 10.36 +/- 3.36 vs 8.64 +/- 3.15, 20.84 +/- 23.89 vs 8.56 +/- 7.48, and 0.038 +/- 0.007 vs 0.032 +/- 0.004, respectively, and significantly higher than the mean values of control group (p < 0.05). However, no correlation was found between CCA-IMT and CRP, SAA, Hcy, and Lp-a. Twenty-nine patients had M694V mutation, and 13 patients had other mutations. There was no correlation between CCA-IMT and MEFV mutation subgroups. In conclusion, because of the nature of the disease, FMF patients should be considered to have an increased risk of early vascular alteration and atherosclerosis. For this reason, CCA-IMT measurement can be recommended as a noninvasive and early diagnostic method.

A case of homozygous familial hypercholesterolemia with focal segmental glomerulosclerosis.

Familial hypercholesterolemia (FH) is a common autosomal dominant inherited disorder characterized by increased levels of circulating plasma low-density lipoprotein cholesterol (LDL-C), tendon xanthomas, and premature atherosclerotic cardiovascular disease. Homozygous FH occurs in only one in a million people. Focal segmental glomerulosclerosis (FSGS) is clinically characterized by proteinuria, which is marked in the majority of cases and accompanied by nephrotic syndrome, high incidence of hypertension, and progression to renal failure. To our knowledge, we herein report for the first time a case of homozygous FH associated with FSGS. A seven-and-a-half-year-old boy was referred to our hospital due to cutaneous xanthomata and growth retardation. He had multiple nodular yellowish cutaneous xanthomatous lesions each 1 cm in size over his knees and sacral region. Laboratory data included cholesterol level of 1,050 mg/dl, low density lipoprotein cholesterol (LDL-C) 951 mg/dl, high-density lipoprotein cholesterol (HDL-C) 29 mg/dl, triglycerides 168 mg/dl, total protein 6.3 g/dl, and albumin 3.2 g/dl. Urinary protein excretion was 78 mg/m(2) per hour. A percutaneous renal biopsy was performed, and histological findings showed FSGS. Treatment with cholestyramine and atorvastatin was unsuccessful in terms of lowering lipids, and he was placed on weekly sessions of plasmapheresis. Total cholesterol was reduced from 1,050 mg/dl to 223 mg/dl, LDL-C from 951 mg/dl to 171 mg/dl, and urinary protein excretion from 78 mg/m(2) per hour to 42 mg/m(2) per hour after eight sessions of plasmapheresis. It is our belief that plasmapheresis is a treatment of choice in patients with FSGS associated with FH.