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Background: Autosomal dominant polycystic kidney disease (ADPKD) causes the development of renal cysts and leads to a decline in renal function. Limited guidance exists in clinical practice on the use of tolvaptan. A decision algorithm from the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Working Groups of Inherited Kidney Disorders and European Renal Best Practice (WGIKD/ERBP) has been proposed to identify candidates for tolvaptan treatment; however, this algorithm has not been assessed in clinical practice. Methods: Eighteen-month cross-sectional, unicenter, observational study assessing 305 consecutive ADPKD patients. The ERA-EDTA WGIKD/ERBP algorithm with a stepwise approach was used to assess rapid progression (RP). Subsequently, expanded criteria based on the REPRISE trial were applied to evaluate the ­impact of extended age (≤55 years) and estimated glomerular filtration rate (eGFR; ≥25 mL/min/1.73 m2). Results: Historical eGFR decline, indicative of RP, was fulfilled in 26% of 73 patients who were candidates for RP assessment, mostly aged 31–55 years. Further tests including ultrasound and MRI measurements of kidney volume plus genetic testing enabled the evaluation of the remaining patients. Overall, 15.7% of patients met the criteria for rapid or likely RP using the algorithm, and the percentage increased to 27% when extending age and eGFR. Conclusions: The ERA-EDTA WGIKD/ERBP algorithm provides a valuable means of identifying in routine clinical practice patients who may be eligible for treatment with tolvaptan. The impact of a new threshold for age and eGFR may increase the percentage of patients to be treated.

Purpose: To compare the efficacy and patients' tolerance of a new mixed biphasic oral contrast solution with routine biphasic oral contrast agent in magnetic resonance (MR) enterography (MRE). Materials and Methods: Thirty-seven patients (group 1) had MRE with the new mixture, whereas 14 patients (group 2) had MRE with biphasic oral contrast agent (lactulose). Magnetic resonance enterography images were evaluated by 2 experienced radiologists. Each intestinal segment was evaluated for luminal distension (LD), distinction from the surrounding tissue (wall conspicuity), and the confidence of radiologist for evaluation of the specified segment (radiological evaluation confidence). Comparisons between the 2 groups were performed using the Mann-Whitney U test. Interrater and intrarater agreement values were obtained. In addition, patients' acceptability and tolerance were assessed. Results: The new mixture was more effective than the oral contrast agent used in group 2 for LD, wall conspicuity, and radiological confidence. The values of interrater and intrarater agreement in scoring LD, wall conspicuity, and radiological confidence were generally moderate. Conclusion: Our new mixture allowed good-quality enterographic images, and this solution was well tolerated by patients. In addition, this mixture is useful for evaluation of small bowels and colonic segments. We suggest the use of it for enterographic examinations.

article i nfo Ciliary defects lead to various diseases, such as primary ciliary dyskinesia (PCD) and polycystic kidney disease (PKD). We isolated a medaka mutant mii, which exhibits defects in the left-right (LR) polarity of organs, and found that mii encodes dynein axonemal intermediate chain 2a (dnai2a). Ortholog mutations were recently reported to cause PCD in humans. mii mutant embryos exhibited loss of nodal flow in Kupffer's Vesicle (KV), which is equivalent to the mammalian node, and abnormal expression of the left-specific gene. KV cilia in the mii mutant were defective in their outer dynein arms (ODAs), indicating that Dnai2a is required for ODA formation in KV cilia. While the mii mutant retained motility of the renal cilia and failed to show PKD, the loss of dnai2a and another dnai2 ortholog dnai2b led to PKD. These findings demonstrate that Dnai2 proteins control LR polarity and kidney formation through regulation of ciliary motility.

Von Hippel-Lindau disease (VHL) is an autosomal dominant inherited cancer syndrome. The disease was diagnosed in three patients: a 22-year-old woman who presented with decreased vision due to retinal angiomatosis and in whom a renal carcinoma was diagnosed five years later at a routine VHL analysis, a man aged 44 who died with bilateral renal cysts and clear-cell carcinomas with metastases, who had a positive family history but in whom no regular control investigations had been performed, and a 31-year-old man who also had a positive family history, but who presented with epididymal cystadenoma and who in the subsequent decades developed cerebral and renal neoplasms that all were detected at routine examinations and subsequently removed. These case histories emphasize the importance of: (a) early recognition of patients presenting with a 'sporadic VHL-like' tumour, (b) frequent screening and early treatment of VHL patients and (c) nephron sparing surgery in VHL patients. The prognosis and quality of life of patients with VHL disease has significantly increased by early detection and treatment of asymptomatic tumours, in particular in the eye and kidney.

There is a group of inherited cystic nephropathies that are characterized by juvenile onset recessive inheritance (familial juvenile nephronophthisis, FJN) or by adult onset dominant inheritance (medullary cystic disease, MCD) and share similar clinico-pathological presentation to the extent that they are usually grouped together under the term FJN/MCD complex. The main symptoms consist of renal cyst formation in the medulla or the corticomedullary junction and salt wasting. Although earlier reports had suggested that one single gene may be responsible for this pathology, recent reports have shown that the FJN complex itself comprises a genetically heterogeneous group. Here we are presenting two large Cypriot families that segregate autosomal dominant medullary cystic kidney disease (ADMCKD) with hyperuricemia and gout and with very late age of onset (mean 62.2 and 51.5 years). We performed DNA linkage mapping using highly polymorphic microsatellite markers and found linkage to marker locus D1S1595 at 1q21 with a two-point lod score of 6.45 at θ = 0.00. Analysis of haplotypes and of critical recombinants enabled confinement of the disease locus within an ~ 8 cM region between marker loci D1S498 and D1S2125. FISH mapping with a large P1 clone confirmed the physical localization within 1q21. The two families share the same disease haplotype, thus suggesting their relationship through a common ancestor and the possible existence of a single ADMCKD-causing mutation within these families. To our knowledge this is the first genetic locus identified to cause FJN/MCD pathology of the dominant adult type. 7 905 911 Cited By :99

Acute heart failure following itraconazole use: a case report A 44year old woman was admitted to the cardiology department of the Medical Centre Leeuwarden, the Netherlands, with acute heart failure. She had developed dyspnoea that began one week after start of itraconazole oral therapy once daily 200 mg for treatment of onychomycosis. Salbutamol and prednisolone were prescribed, but this gave no improvement in the symptoms. She stopped after four weeks with the itraconazole treatment, but seven weeks later she was admitted to the cardiology department with heart failure NYHA class 4. The electrocardiogram showed a moderate left ventricular function, while heart valves and coronary arteries showed no abnormalities in morphology and function. Troponin levels were not elevated. Treatment with candesartan and furosemide started, supported by a reduced intake of fluids and a low sodium diet. Two weeks later the patient was again admitted with dyspnoea. Seven months after the start of the symptoms the patient was still using candesartan. Besides kidney cysts (since 1985) the patient had no other comorbidities and used no medication. Her kidney function was stable for many years [creatinine 62 μmol/L, eGFR 85 mL/(min·1.73 m2)]. The Naranjo score was 4, which indicates itraconazole being a 'possible' cause of the acute heart failure. In several articles itraconazole is mentioned as possible cause of heart failure, but the mechanism is unknown. The side effect does not seem to be related to azole antimycotics in general. In patients with acute heart failure and/or dyspnoea and itraconazole usage, the side effect has to be taken into account in the differential diagnosis as a possible cause.

Significant variation in the course of autosomal dominant polycystic kidney disease (ADPKD) within families suggests the presence of effect modifiers. Recent studies of the variation within families harboring PKD1 mutations indicate that genetic background may account for 32 to 42% of the variance in estimated GFR (eGFR) before ESRD and 43 to 78% of the variance in age at ESRD onset, but the genetic modifiers are unknown. Here, we conducted a high-throughput single-nucleotide polymorphism (SNP) genotyping association study of 173 biological candidate genes in 794 white patients from 227 families with PKD1. We analyzed two primary outcomes: (1) eGFR and (2) time to ESRD (renal survival). For both outcomes, we used multidimensional scaling to correct for population structure and generalized estimating equations to account for the relatedness among individuals within the same family. We found suggestive associations between each of 12 SNPs and at least one of the renal outcomes. We genotyped these SNPs in a second set of 472 white patients from 229 families with PKD1 and performed a joint analysis on both cohorts. Three SNPs continued to show suggestive/significant association with eGFR at the Dickkopf 3 (DKK3) gene locus no SNPs significantly associated with renal survival. DKK3 antagonizes Wnt/β-catenin signaling, which may modulate renal cyst growth. Pending replication, our study suggests that genetic variation of DKK3 may modify severity of ADPKD resulting from PKD1 mutations. Copyright © 2010 by the American Society of Nephrology. 21 1510 1520 Cited By :31

Objective: We wanted to assess the long-term results of cyst ablation with using N-butyl cyanoacrylate (NBCA) and iodized oil in patients with autosomal dominant polycystic kidney disease (ADPKD) and symptomatic cysts. Materials and Methods: Cyst ablation using a mixture of NBCA and iodized oil was performed in 99 cysts from 21 patients who had such symptoms as abdominal distension and pain. The collapse or reaccumulation of the ablated cysts after the procedure was assessed during the follow-up period of 36 to 90 months. The treatment effects, including symptom relief, and the clinical data such as the blood pressure and serum creatinine levels were also assessed, together with the complications. Results: The procedure was technically successful in all 99 cysts from the 21 patients. Any procedure-related significant complications were not detected. Seventy-seven of 99 cysts (78%) were successfully collapsed on the follow-up CT. Twenty-two cysts showed reaccumulation during long-term follow-up period. The clinical symptoms were relieved in 17 of the 21 patients (76%). Four of 12 patients (33%) with hypertension and two of six patients (33%) with azotemia were improved. End stage renal disease (ESRD) occurred in six of the 21 patients (28%) during the follow-up period. The mean age of ESRD in our patients was 57 years. The mean time interval for the development of ESRD was 19 months. Conclusion: Ablation using a mixture of NBCA and iodized oil may be an effective, safe method for obtaining symptom relief in patients with ADPKD.

We report an unusual death of an apparently healthy 56-year-old male due to massive hemorrhage caused by rupture of an artery in the wall of a solitary renal cyst, possibly after a relatively minor trauma. Fatalities due to spontaneous or posttraumatic rupture of renal cysts are extremely rare but can represent a potential danger for people with acquired cystic kidney disease. Our report describes results of the forensic investigation and discusses possible mechanisms of the rupture.

La diferenciación entre los quistes renales benignos, que no requieren tratamiento quirúrgico, y aquellos que requieren exploración quirúrgica en ocasiones es difícil. El tratamiento mediante cirugía laparoscópica (Decorticación quística - Nefrectomía laparoscópica parcial o radical según los hallazgos) se establece día a día como el tratamiento de elección en los pacientes con quiste Renal atípico o complejo Grado III y IV de Bosniak, así como en los quistes renales tipo I/II sintomáticos y en determinados pacientes con quiste renal etiquetado como IIF de Bosniak. Presentamos un caso clínico en el que se halla carcinoma renal de células claras tras decorticación laparoscópica de un quiste Grado II de Bosniak, con realización posterior de nefrectomía radical laparoscópica. The difference between the simple renal cysts, that doesn't require surgical treatment, and those that need it, sometimes is difficult. The laparoscopic surgical treatment (laparoscopic cyst decortication -laparoscopic partial nefrectomy or radical laparoscopic nefrectomy) its becoming the gold standard technique, recommending this procedure in Bosniak cyst type III or IV, and in the symptomatic renal cyst type I/II and in any patients with Bosniak cyst renal II. We present a case report in which a renal cell carcinoma was found after laparoscopic cyst decortication of Bosniak cyst type II with laparoscopic radical nefrectomy posteriorly.

The purpose of this study was to evaluate the capability and the reliability of diffusion-weighted MRI in the evaluation of normal kidney and different renal lesions. 39 patients (10 normal volunteers and 29 patients with known renal lesions) underwent MRI of the kidneys by using a 1.5 T superconducting magnet. Axial fat suppressed turbo spin echo (TSE) T(2) and coronal fast field echo (FFE) T(1) or TSE T(1) weighted images were acquired for each patient. Diffusion-weighted (DW) images were obtained in the axial plane during breath-hold (17 s) with a spin-echo echo planar imaging (SE EPI) single shot sequence (repetition time (TR)=2883 ms, echo time (TE)=61 ms, flip angle=90 degrees ), with b value of 500 s mm(-2). 16 slices were produced with slice thickness of 7 mm and interslice gap of 1 mm. An apparent diffusion coefficient (ADC) map was obtained at each slice position. The ADC was measured in an approximately 1 cm region of interest (ROI) within the normal renal parenchyma, the detected renal lesions and the collecting system if dilated. ADC values in normal renal parenchyma ranged from 1.72 x 10(-3) mm(2) s(-1) to 2.65 x 10(-3) mm(2) s(-1), while ADC values in simple cysts (n=13) were higher (2.87 x 10(-3) mm(2) s(-1) to 4.00 x 10(-3) mm(2) s(-1)). In hydronephrotic kidneys (n=6) the ADC values of renal pelvis ranged from 3.39 x 10(-3) mm(2) s(-1) to 4.00 x 10(-3) mm(2) s(-1). In cases of pyonephrosis (n=3) ADC values of the renal pelvis were found to be lower than those of renal pelvis of hydronephrotic kidneys (0.77 x 10(-3) mm(2) s(-1) to 1.07 x 10(-3) mm(2) s(-1)). Solid benign and malignant renal tumours (n=7) showed ADC values ranging between 1.28 x 10(-3) mm(2) s(-1) and 1.83 x 10(-3) mm(2) s(-1). In conclusion diffusion-weighted MR imaging of the kidney seems to be a reliable way to differentiate normal renal parenchyma and different renal diseases. Clinical experience with this method is still preliminary and further studies are required.

Acute heart failure following itraconazole use: a case report A 44year old woman was admitted to the cardiology department of the Medical Centre Leeuwarden, the Netherlands, with acute heart failure. She had developed dyspnoea that began one week after start of itraconazole oral therapy once daily 200 mg for treatment of onychomycosis. Salbutamol and prednisolone were prescribed, but this gave no improvement in the symptoms. She stopped after four weeks with the itraconazole treatment, but seven weeks later she was admitted to the cardiology department with heart failure NYHA class 4. The electrocardiogram showed a moderate left ventricular function, while heart valves and coronary arteries showed no abnormalities in morphology and function. Troponin levels were not elevated. Treatment with candesartan and furosemide started, supported by a reduced intake of fluids and a low sodium diet. Two weeks later the patient was again admitted with dyspnoea. Seven months after the start of the symptoms the patient was still using candesartan. Besides kidney cysts (since 1985) the patient had no other comorbidities and used no medication. Her kidney function was stable for many years [creatinine 62 μmol/L, eGFR 85 mL/(min·1.73 m2)]. The Naranjo score was 4, which indicates itraconazole being a 'possible' cause of the acute heart failure. In several articles itraconazole is mentioned as possible cause of heart failure, but the mechanism is unknown. The side effect does not seem to be related to azole antimycotics in general. In patients with acute heart failure and/or dyspnoea and itraconazole usage, the side effect has to be taken into account in the differential diagnosis as a possible cause.

Background. Autosomal-dominant medullary cystic kidney disease (ADMCKD), a hereditary chronic interstitial nephropathy, recently attracted attention because of the cloning or mapping of certain gene loci, namely NPHP1, NPHP2 and NPHP3 for familial juvenile nephronophthisis (NPH) and MCKD1 and MCKD2 for the adult form of medullary cystic kidney disease. Our aim was to present and discuss the clinical, biochemical, sonographic and histopathological findings in six large Cypriot families in whom molecular analysis has confirmed linkage to the MCKD1 locus on chromosome 1q21. Methods. The clinical, biochemical, sonographic and histopathological findings in 186 members of six large Cypriot families with ADMCKD-1 are presented. Creatinine clearance was calculated according to the Cockroft-Gault formula and was corrected to a body surface area (BSA) of 1.73 m2. DNA linkage analysis was performed with previously identified flanking polymorphic markers. Results. This disease is characterized by the absence of urinary findings in the vast majority of patients, leading to end-stage renal failure (ESRF) at a mean age of 53.7 years. Hypertension and hyperuricemia are common, especially in males, the former encountered more frequently in advanced chronic renal failure (CRF). Gout has been noted in a small percentage of male patients. Loss of urinary concentrating ability was not a prominent early feature of the disease, while severe natriuresis was observed in a few males toward ESRF. Renal cysts are mainly corticomedullary or medullary, and they are present in about 40.3% of patients and appear more frequently near ESRF. Conclusion. ADMCKD type 1 is a common cause of ESRF among our dialysis population. The disease is difficult to diagnose clinically, particularly in the early stage when renal cysts are not usually present, making them a weak diagnostic finding. A dominant pattern of inheritance and DNA linkage analysis are helpful in the diagnosis of this disease. 62 4 1385 1394 Cited By :37

Von Hippel-Lindau disease (VHL) is an autosomal dominant inherited cancer syndrome. The disease was diagnosed in three patients: a 22-year-old woman who presented with decreased vision due to retinal angiomatosis and in whom a renal carcinoma was diagnosed five years later at a routine VHL analysis, a man aged 44 who died with bilateral renal cysts and clear-cell carcinomas with metastases, who had a positive family history but in whom no regular control investigations had been performed, and a 31-year-old man who also had a positive family history, but who presented with epididymal cystadenoma and who in the subsequent decades developed cerebral and renal neoplasms that all were detected at routine examinations and subsequently removed. These case histories emphasize the importance of: (a) early recognition of patients presenting with a 'sporadic VHL-like' tumour, (b) frequent screening and early treatment of VHL patients and (c) nephron sparing surgery in VHL patients. The prognosis and quality of life of patients with VHL disease has significantly increased by early detection and treatment of asymptomatic tumours, in particular in the eye and kidney.

Autosomal dominant medullary cystic kidney disease (ADMCKD synonym: medullary cystic disease, MCD) is an autosomal dominant kidney disorder, sharing morphological and clinical features with recessive juvenile nephronophthisis (NPH), such as reduced urinary concentration ability and multiple renal cysts at the corticomedullary junction. While in NPH end-stage renal disease (ESRD) occurs in adolescence, ADMCKD leads to ESRD in adulthood. Recently a gene locus for ADMCKD has been localized to chromosome 1q21 in two large Cypriot families. This prompted us to examine linkage in three ADMCKD-families, using the same set of polymorphic microsatellite markers spanning the critical region on chromosome 1q21. Haplotype analysis revealed that none of the three families showed linkage to this locus, thus demonstrating evidence for genetic locus heterogeneity. Additional linkage analysis studies need to be performed in order to identify further gene loci cosegregating with this autosomal dominant kidney disorder. 13 1955 1957 Cited By :25

Autosomal dominant polycystic kidney disease (ADPKD), is a heterogeneous disorder, primarily characterized by the formation of cysts in the kidneys, and the late development in life of progressive chronic kidney failure. Three genes are implicated in causing ADPKD. One on chromosome 16, PKD1, accounts for 85-90% of all cases, and the PKD2 gene on chromosome 4 accounts for the remainder. A very rare third locus is still of unknown location. We used PKD1- and PKD2-linked polymorphic markers to make the diagnosis of ADPKD in young presymptomatic members in affected families. We showed that in young members of families where clinical diagnosis cannot be definitively established, molecular linkage analysis can assist clinicians in the diagnosis. In one family a 24-year old had one cyst on the right kidney however, molecular analysis showed clearly that he had inherited the normal haplotype. In another family, in one part of the pedigree there was co-inheritance of the disease with a PKD1-linked haplotype which originated in a non-affected 78-year-old father. Analysis with PKD2-linked markers excluded this locus. The data can be explained in one of two ways. Either this family phenotype is linked to a third locus, or the proband was the first affected person, most probably because of a novel mutation in one of her father's chromosomes. In conclusion, the combined use of markers around the PKD1 and the PKD2 locus provides more definitive answers in cases where presymptomatic diagnosis is requested by concerned families. 50 10 18 Cited By :15