Clinical and histopathological characteristics of COL4A3 c.2881+1G>A variant causing Alport spectrum disorders in Croatian population.

Alport syndrome (AS) and thin basement membrane nephropathy (TBMN) are part of the spectrum of kidney disorders caused by pathogenic variants in α3, α4, or α5 chains of the collagen type IV, the major structural component of the glomerular basement membrane (GBM). Using targeted next-generation sequencing (NGS), 34 AS/TBMN patients (58.8% male) from 12 unrelated families were found positive for heterozygous c.2881+1G>A variant of the COL4A3gene, that is considered disease-causing. All patients were from the continental or island part of Croatia. Clinical, laboratory, and histopathological data collected from the medical records were analyzed and compared to understand the clinical course and prognosis of the affected patients. At the time of biopsy or first clinical evaluation, the mean age was 31 years (median: 35 years; range: 1 - 72 years). Hematuria was present in 33 patients (97.1%) and 19 (55.9%) patients had proteinuria. There were 6 (17.6%) patients with hearing loss, 4 (11.8%) with ocular lesions, and 11 (32.4%) with hypertension. Twenty-three (67.6%) patients had proteinuria at follow-up, and 5 (14.7%) patients with the median age of 48 years (range: 27-55) progressed to kidney failure, started dialysis, or underwent kidney transplantation. Of the 13 patients who underwent kidney biopsy, 4 (30.8%) developed focal segmental glomerulosclerosis (FSGS), and 8 (66.7%) showed lamellation of the GBM, including all patients with FSGS. It is essential to conduct a detailed analysis of each collagen type IV genetic variant to optimize the prognosis and therapeutic approach for affected patients.

Resistant and Relapsing Collapsing Glomerulopathy Successfully Treated with Rituximab-A Case Report.

Collapsing glomerulopathy (CG) or collapsing focal segmental glomerulosclerosis (cFSGS) is an aggressive disease with a high tendency of progression to end-stage renal disease due to common resistance to conventional immunosuppressants. Rituximab (RTX), a monoclonal antibody against CD20 B cells, showed some benefit in the treatment of CG. We are reporting about female patients with an idiopathic form of CG presenting with nephrotic syndrome (NS) and renal insufficiency resistant to several immunosuppressive agents such as steroids (ST), calcineurin inhibitors (CNI), and cyclophosphamide (CYC). This multidrug-resistant disease responded to RTX with complete remission. Forty-four months after initial RTX administration, a relapse of CG with severe NS and acute renal insufficiency occurred. Repeated application of RTX led to complete remission again. To the best of our knowledge, we are reporting the first case of the relapsing multidrug-resistant form of CG, which responded to RTX. Current data about the treatment of CG with RTX is lacking and is based on rare case reports and small case series. Thus, our report can contribute to determining the role of RTX in the treatment of CG.

[Transplantation and retransplantation--impact on emotional state]. / Transplantacija i retransplantacija--utjecaj na emocionalno stanje.

In our clinical practice, we are often faced with emotional difficulties of transplanted patients. Most are due to anxiety, difficulty in integrating newly recruited organ as its own, feeling of guilt, and difficulties with personal experience of self. Despite common presence of emotional difficulties, many studies describe improvement in the quality of life of transplant patients. However, the quality of life is deteriorating again in case of transplant rejection. In such situations, restlessness develops along with losing control over their own lives, a sense of failure, hopelessness and lack of prosperity ideas. Complex emotional experiencing is very important in strengthening the patient's psychological health and personality, thus achieving better treatment compliance in general.

[Cardiac valves calcifications in dialysis patients]. / Kalcifikacije srcanih zalistaka kod pacijenata na kronicnoj hemodijalizi.

Chronic kidney disease (CKD) patients, especially those with end-stage renal disease (ESRD), are at much higher risk of cardiovascular disease (CVD) than the general population. High serum phosphorus (P) level play important role in pathogenesis of cardiovascular calcifications and is a frequent and important cardiovascular risk factor in patients with CKD. We aimed to investigate the association of serum levels of C-reactive protein (CRP), parathyroid hormon (PTH). calcium phosphorus product (CaxP) with cardiac valves calcifications (VC) in patients on hemodialysis (HD). We investigated for VC using colour Doppler echocardiography. VC were considered present if mitral annular calcifications and/or aortic annular calcifications were visualized. We divided patients in two groups. VC negative group (VC-) were patients with absence of VC. Patients with presence of VC were VC positive (VC+). CRP mean levels in two samples were higher in VC+ group than in VC- group (17.0 vs 3.4mg/L) and (17.1 vs 4.0 mg/L) p<0.0001. CaxP mean level in both samples was higher in VC+ group than in VC- group, 4.8 vs 4.2 (p=0.0219) and 5.0 vs 4.3 (p=0.0078). We also made analysis of absolute highest levels of three samples of CRP (CRPmax) between groups. CRPmax was higher in VC+ group than in VC- group, 19.5 vs 9.7 mg/L, (p=0.0045). We made analysis of absolute higher levels of two samples of Ca x P (CaxPmax) between groups. CaxPmax was higher in VC+ group than in VC- group, 5.2 vs 4.4 (p=0.0014). We found cardiac valve calcifications in 40 percent of patients on hemodialysis. We found that patients with correlation between PTH level, CRP level, CaxP product and cardiac valve calcifications have higher serum levels of PTH and CRP. We also found that CaxP product is higher in patients with cardiac valve calcifications. We didn't find correlation between age, dialysis duration, BMI and cardiac valve calcifications. These findings support careful monitoring of calcium metabolisum in end stage renal disease to reduce valvular cacifications and the risk of cardiovascular disease.

[Anaemia in chronic kidney disease: target haemoglobin concentration in patients treated with erythropoesis stimulating agents]. / Anemija kronicne bubreine bolesti: ciljne vrijednosti hemoglobina za bolesnike lijecene pripravcima koji stimuliraju eritropoezu.

UNLABELLED: Dialysis Center, Department of Internal Medicine, Zadar General Hospital, Zadar, Croatia Anaemia is most often manifested in the third stage of chronic kidney disease and is closely related to morbidity and mortality of these patients, and it has a proven negative effect on the quality of life. It is therefore important to treat these patients early, especially the most vulnerable groups such as diabetics, and we need clearly defined guidelines as well as target haemoglobin concentration to treat these patients. The guidelines are the result of investigations and conclusions of professional societies, and legal regulations and insurance agencies use professional societies guidelines for their purposes. Target haemoglobin concentration that is recommended in American, European and our national guidelines is within 120 to 120 g/L and should not be higher. Asmall number of patients are able to maintain this concentration, because of the comorbide conditions and other factors that effect haemoglobin stability. Poor outcomes are possible in patients whose haemoglobin concentration is higher than recommended but mortality is also higher in patients whose haemoglobin concentration is lower than the target for a longer period of time. CONCLUSION: the lowest mortality as seen in all the studies and meta analyses is in patients whose haemoglobin concentration is within the target range. Haemoglobin concentration variability stays a constant challenge in investigational and clinical practice.