Hypertension and nephrology

[Genetics of isolated steroid-resistant nephrotic syndrome - results of the two decades around the turn of the millennium]

TORY Kálmán, KERTI Andrea, REUSZ György

DECEMBER 20, 2011

Hypertension and nephrology - 2011;15(05)

[Childhood steroid-resistant nephrotic syndrome (SRNS) is a devastating clinical condition which progresses to end-stage renal disease in 30-40% of the cases after a follow up of 10 years. Based on its etiology, two forms can be distinguished, an immune and a genetic form. During the last two decades, mutations of ten genes - encoding mainly podocyte proteins - were identified in the latter group. As the treatment in the immune and genetic forms are different, and only the identification of the causative mutation can reliably distinguish them, it is important to be familiarized with the genotype-phenotype correlations. The aim of the present review is to summarize our current knowledge on the phenotypes linked to the identified genes.]

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Hypertension and nephrology

[Antihypertensive therapy in patients with COPD - the significance of nebivolol]

FARSANG Csaba

[The occurrence of hypertension associated with chronic obstructive pulmonary disease (COPD) is increasing. Recognising COPD is important in order to choose the appropriate antihypertensive drugs. Anti-hypertensive drugs that can be used to treat patients with hypertension and COPD include diuretics, ACE-inhibitors, angioten-sine receptor blockers (AT1 receptor antagonists) and calcium antagonists, as well as cardioselective beta blockers, as these drugs decrease total and cardiovascular mortality. Of these agents, the importance of the most cardioselective one, nebivolol should be stressed, as this drug has no clinically significant effect on parameters of respiratory function, and, through its additional effects (namely by increasing the synthesis of NO), it has a beneficial effect on COPD-related deterioration of respiratory functions, haemodynamic alterations (cor pulmonale) and local factors that participate in the respiratory inflammation and endothelial dysfunction.]

Hypertension and nephrology

[Similarities and differences in the renal effects of statins]

ÁBRAHÁM György

[By efficiently reducing serum cholesterol level, statins significantly decrease both cardiovascular morbidity and mortality. Decreasing LDL-cholesterol level by 1% reduces coronary mortality risk by 1%, whereas increasing HDL-cholesterol level by 1% reduces the risk by 3%. At the same time, renal failure significantly increases cardiovascular events and/or mortality compared with the population mean. It is an exciting question whether statins are able to prevent and decelerate the deterioration of kidney function deterioration, preserve GFR and decrease albuminuria. Depending on the strength of their effect, statins have different cholesterollowering capacity (rosuvastatin and atorvastatin are especially effective). An important question is whether these differences can be detected in the renal function as well. The results of experimental data and major clinical trials (e.g. AURORA, PLANET I-II, SHARP) are often controversial. Nevertheless, statin therapy has advantages for patients with kidney diseases, although to a lesser extent than it has in the normal population.]

Hypertension and nephrology

[Association of body composition and mortality in patients on maintenance dialysis and on waitlist and after kidney transplantation]

UJSZÁSZI Ákos, KALANTAR-ZADEH Kamyar, MOLNÁR Miklós Zsolt

[Overweight [body mass index (BMI) = 25-30 kg/m2] and obesity (BMI ≥30 kg/m2) are epidemic in both developed and developing countries. Obesity has been recognized as risk factor for the development and progression of chronic kidney disease and is associated with increased cardiovascular risk and poor survival. Almost 2/3 of maintenance hemodialysis patients die within five years of commencing dialysis treatment. Although patients on the waitlist having less severe comorbidities than their non-listed counterparts, the death rate remains high while it can take years for an organ donation. In patients with end stage renal disease (ESRD) undergoing maintenance hemodialysis an “obesity paradox” has been consistently reported, i.e., a high BMI is incrementally associated with better survival. Overweight and obesity are highly prevalent in patients at the time of kidney transplantation. Indeed, most transplant centers in US may suspend wait-listing of obese patients with a BMI above 30 or 35 kg/m2 and refer them for weight reduction procedures such as bariatric surgery as a contingency for the transplant surgery. The effect of pre- and post-transplant obesity in kidney transplanted patients on long-term graft and patient survival has not been well established. We have reviewed and summarized salient recent data pertaining to body composition and clinical outcomes about the association of survival and body composition in transplant-waitlisted dialysis patients and kidney transplanted recipients. ]

Hypertension and nephrology

[Association between complications of percutaneous kidney biopsy and histological diagnosis ]

FISI Viktória, MAZÁK István, DEGRELL Péter, HALMAI Richárd, MOLNÁR Gergő A., FEHÉR Eszter, NÉMETH Kinga, PINTÉR István, KOVÁCS Tibor, WITTMANN István

[Background: Percutaneous renal biopsy is an essential tool in diagnosis and prognosis of renal diseases. It is well-known that this method has potential complications. The connection between complication occurrence related to renal biopsies and histological diagnoses of the biopsy specimen was analyzed in the present study. We also analyzed the distribution of diagnoses in our population. Methods: In this retrospective survey, 353 patients undergoing renal biopsy was studied. Biopsies were performed after marking the site of puncture with ultrasound imaging. Influence of diagnoses and clinical parameters on complications was evaluated. Results: We found a complication rate of 44.5%. In patients with diabetic nephropathy (likelihood ratio (LR) 0.44) or acute tubular necrosis (LR 0.38) a significantly lower rate of complications was found, while patients with thin basement membrane syndrome had more than 6-fold higher risk for evolvement of intrarenal haemorrhage. Patients with acute interstitial nephritis (LR 3.18) or vasculitis (LR 2.88) have a more than 2-fold risk for arteriovenous shunts while in patients with severe arteriosclerosis the occurrence of this complication was lower (LR 0.46). In rapidly progressive glomerulonephritis, arteriovenous shunts evolved also in a significantly higher rate. Conclusion: Patients with vasculitis, rapidly progressive glomerulonephritis, thin basement membrane syndrome or acute interstitial nephritis should be monitored more carefully after renal biopsy due to the significantly higher risk for complications. ]

Hypertension and nephrology

[Remembering Professor Péter Bálint on his 100th Birth Anniversary ]

BARTHA Jenő

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[Parkinson’s disease is a promising target of applying personalized medicine. For this purpose it is crucial to reveal the genetic and environmental factors, which contribute to the disease, also to collect epidemiologic data and to preserve the patients samples and data in a proper biobank. In our investigation we examined the prevalence of the most frequent Parkinson’s disease causing LRRK2 G2019S mutation in a Hungarian Parkinson-patient group. From 120 patients, we haven’t detected this substitution in anyone. Our investigation suggest that the mutation LRRK2 G2019S may be a rare cause of Parkinson disease in the Hungarian population.]

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[In this article we review epilepsies with monogenic inheritance. Most of these diseases are caused by abnormal function of ligand- and voltage gated ion channels caused by a genetic defect, therefore belonging to the channelopathies. From the inherited epilepsies the genetics of the autosomal dominant partial epilepsies is clarified the best. Mutations of the nicotinic acetylcholine receptor subunits are found in familial nocturnal frontal lobe epilepsy, while defects in the voltage gated potassium channels (KCNQ2 and KCNQ3) have been identified in benign familial neonatal convulsions. Familial temporolateral epilepsy was associated with mutations of a tumor suppressor gene. From the generalized epilepsies, the syndrome of generalized epilepsy with febrile seizures plus (GEFS+) can be caused by mutations of the sodium channel subunits and of the GABAA receptor subunits. These important results would probably lead to new findings in the genetics of the more common forms of idiopathic generalized epilepsies, which have presumed polygenic origin. Although without definite conclusions, sodium channel and GABA receptor dysfunction is presumed. The accumulated knowledge about channelopathies enables insight to the cellular mechanism of epileptogenesis as well.]

Hypertension and nephrology

[Symptomes and genetics of nephronophthisis]

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[Nephronophthisis is an autosomal recessive, chronic tubulointerstitial nephropathy, responsible for 6-10% of childhood chronic renal failure cases. Its first symptoms, polyuria-polydipsia, anaemia and failure to thrive precede the development of end-stage renal disease by years. Increased echogenicity with loss of corticomedullary differentiation are the key findings on ultrasound, the lack of cysts does not rule out the diagnosis. Histologically, it is characterized by interstitial fibrosis and irregularities of the tubular basal membrane. Genetically, it is highly heterogeneous. Ten nephronophthisis genes have already been identified in 60% of the patients. The encoded proteins - similarly to other proteins mutated in cystic kidney diseases - are localized to primary cilium-basal body-centrosomal complex.]

Clinical Neuroscience

[Genetics and hemostasis in young stroke patients]

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[Background and purpose - The classical risk factors did not explain all the possible ethiology of cerebral stroke. Genetic polymorphisms responsible for thrombophilia were implicated recently as risk factors of stroke. In this geneticoepidemiological study the author’s aim was to analyse the tendency of genetic polymorphisms to cluster in a cohort of young and elderly stroke patients and in healthy subjects in Hungary. Methods - 253 patients with stroke were compared with 173 healthy blood donors on the basis of genetic polymorphisms of platelet GP IIb/IIIa receptor (33 LeuPro), prothrombin gene G20210A, Factor V Leiden mutation, ACE I/D, methylenetetrahydrofolate reductase (MTHFR) and β fibrinogen gene G455A. These data were acquired using PCR. Questionnaires were used to investigate the family history and to determine the risk factor profile. The subtypes of stroke were analysed in a stroke cohort grouped according to different polymorphisms. Results - An increased frequency of GP IIIa heterozygousity was found as compared to a West-European stroke cohort (31% versus 19%). The prothrombin gene variant (2.9% European and 4.8% in Hungary) was also found to increase in frequency. In young stroke patients (age <50) compared with control subjects the odds ratios were higher: in prothrombin gene (OR: 4.9), in Leiden mutation (OR: 1.67), in fibrinogen gene (OR: 1.64) and in MTHFR(+/+) (OR: 1.58). Clustering of two polymorphisms could only be detected in young patients. These clustering polymorphisms were GP IIb/IIIa with prothrombin G20210A variant (OR: 6.74, 95% CI 1.1-18.2) and prothrombin gene variant with MTHFR (OR: 5.3, CI95 1.2-8.3). Conclusion - Selected and clustered genetic polymorphisms of haemostatic factors could be responsible for the high stroke morbidity in Central Europe. The presence and clustering tendency of these factors have been described in young stroke victims.]