Idiopathic Membranous Nephropathy and Treatment Related Complications.

INTRODUCTION: Idiopathic Idiopathic membranous nephropathy (iMN) is an immune-complex mediated renal disease which is usually associated with the nephrotic syndrome (NS). The course of the disease is variable. Some patients maintain normal kidney function with or without a spontaneous remission of proteinuria, while others progress to end-stage renal failure or die from complications related to the nephrotic syndrome. Whether or not to treat a patient with idiopathic membranous nephropathy is still controversial. The controversy is mainly related to the toxicity of the therapy and the variable natural course of the disease-spontaneous remission occurs in 40-50% of patients. AIM: The aim of this study was to describe our experience of treatment of an idiopathic membranous nephropathy (iMN), efficacy and complications rate. CASE REPORT: Our patient was older, mail gender, in high-risk group with persistent proteinuria 10,68 g/day and stable renal function. We have taken these factors into consideration, along with age and other comorbidities, that may significantly elevate the risk of treatment. We chose to start with early treatment, following the Ponticelli's group protocol based on high dose corticosteroids (odd months) alternating with clorambucil (even months) for six months. This treatment was accompanied by the steroid side effects, including hyperglycaemia dependance on insulin therapy and pulmonary thromboembolism despite administered prophylactically low molecular weight heparin. The six-month treatment was successfully completed with the reduction of proteinuria to nephritic values 2,86 g/day, despite many complications. Complete remission of the disease with non-significant proteinuria and with stable renal function was achieved in 14 months which has been maintained for 2 years. CONCLUSION: We suggest that decisions on the timing of start of therapy, whom to treat, best sequence of the use of the various immunosuppressive drugs must be based on an individualized assessment of risks and benefits.

Inflammatory Markers and Procoagulants in Chronic Renal Disease Stages 1-4.

INTRODUCTION: Starting from the point that the chronic kidney disease (CKD) is chronic, inflammatory and hypercoagulable state characterized by an increase in procoagulant and inflammatory markers high cardiovascular morbidity and mortality in these patients could be explained. AIM: The aim of the research was to monitor inflammatory markers and procoagulants in various stages of kidney disease (stage 1-4). MATERIALS AND METHODS: The research included 120 subjects older than 18 years with CKD stages 1-4 examined and monitored in Clinic of Nephrology, University Clinical Centre Sarajevo over a period of 24 months. The research included determining the following laboratory parameters: serum creatinine, serum albumin, C-reactive protein, leukocytes in the blood, plasma fibrinogen, D-dimer, antithrombin III, coagulation factors VII (FC VII) and coagulation factor VIII (FC VIII). RESULTS: With the progression of kidney disease (CKD stages 1-4), there was a significant increase of inflammatory and procoagulant markers: CRP, fibrinogen and coagulation factor VIII, and an increase in the average values of leukocytes and a reduction in the value of antithrombin III, but without statistical significance. Also, there were no significant differences in the values of D-dimer and coagulation factor VII. CONCLUSION: The progression of kidney disease is significantly associated with inflammation, which could in the future be useful in prognostic and therapeutic purposes. Connection of CKD with inflammation and proven connection of inflammation with cardiovascular risk indicates the potential value of some biomarkers, which could in the future identify as predictors of outcome and could have the benefit in the early diagnosis and treatment of cardiovascular disease in CKD.

Renal Function Outcome Prognosis in Septic and Non-septic Acute Kidney Injury Patients.

AIM: The objective of this study was to evaluate prognostic impact of clinical factors on outcome of renal function in septic and non-septic acute kidney injury (AKI) patients. METHODS: The prospective, observational, clinical study was performed at Nephrology Clinic and Clinic for Infectious Diseases, University Clinical Centre Sarajevo. One hundred patients with diagnosis of AKI were enrolled in the study, and divided into two groups: septic and non-septic AKI patients. Clinical parameters included causes and type of AKI, pre-existing comorbidities and different treatment modalities. Patients were followed up until discharge or death. Renal function outcome was defined by creatinine clearance values at discharge. RESULTS: Septic AKI patients had significantly longer hospital stay (p=0.03), significantly worse renal function outcome (p<0.001), and higher burden of comorbidities (70.6% vs. 60.6%), compared to non-septic patients. Septic AKI patients were almost three times less likely to receive renal replacement therapy (8.8% vs. 24.4%) and they had significant delay in initiation of dialysis (p=0.03). By multivariate analysis, sepsis (95% CI 0.128-0.967, p=0.043) and hypertension (95% CI 0.114-0.788, p=0.015) were independent predictors of adverse renal function outcome in AKI patients. Postrenal type of AKI was independent predictor of renal function recovery in non-septic AKI patients (95% CI 1.174-92.264, p=0.035), while Failure, as third class of AKI, was independent predictor of non-recovered renal function only in septic AKI patients (95% CI 0.026 to 0.868, p=0.034). CONCLUSION: Septic AKI patients are clinically distinct compared to non-septic AKI patients with different prognostic factors and poorer renal function outcome.

Clinical analysis of etiology, risk factors and outcome in patients with acute kidney injury.

INTRODUCTION: Acute kidney injury is characterized by a rapid loss of renal excretory function with the increase of nitrogen compounds in the blood and with different outcome. OBJECTIVE: Since descriptions of the risk factors and sequelae of acute kidney injury (AKI) remain relatively limited, the objective of this study was to determine etiology and clinical characteristics of AKI, as well as risk factors for adverse outcome of renal function and death in AKI patients. METHODS: We retrospectively studied a cohort of 84 adult AKI patients admitted to Nephrology Clinic in University Clinical Centre Sarajevo during period 2012-2014. Demographic, laboratory and clinical parameters were retrieved. The in-hospital and 6 months mortality were recorded. Renal function outcome was defined 3 months following discharge. RESULTS: Majority of patients were older (median age 73.5 years) with great severity of AKI (Stage III in 78.5% of cases) and high burden of comorbidities (mean Charlson comorbidity index, CCI score 6.4±3.05). The most common causes of AKI were acute interstitial nephritis (16.7%), heart failure (15.5%), gastroenterocolitis (13.1%), and sepsis (12%). Renal function recovery was recorded in 48.8% of patients, with prevalence of 10.7% of intrahospital mortality and 37.3% of 6 months mortality. Risk factors for poor outcome of renal function and mortality in AKI patients were increasing age and higher CCI score, while protective factor was higher diuresis. Sepsis proved to be risk factor for death.

Serum cystatin C - marker of inflammation and cardiovascular morbidity in chronic kidney disease stages 1-4.

AIM: The aim of the research was to compare the relationship between inflammatory biomarkers and procoagulants with kidney function assessed by using cystatin C, serum creatinine, and eGFR and determine the sensitivity of cystatin C, serum creatinine and eGFR to total cardiovascular morbidity in patients with CKD stages 1-4. METHODS: The research included 120 patients older than 18 years with CKD stages 1-4 monitored over a period of 24 months. RESULTS: Serum cystatin C correlates with fibrinogen (p<0.01), serum albumin (p<0.01), D-dimer (p<0.05), antithrombin III (p<0.01) strongly in relation to the evaluation of kidney function based on serum creatinine and eGFR. By following cystatin C, creatinine and eGFR with comparison of ROC to total cardiovascular morbidity, the highest sensitivity in relation to the presence of cardiovascular morbidity shows cystatin C, then eGFR and the lowest, creatinine, with a significant difference between cystatin C and serum creatinine (p<0.05). CONCLUSION: Serum cystatin C is more strongly correlated with some biomarkers (fibrinogen, serum albumin, D-dimer, antithrombin III), while simultaneously showing a stronger sensitivity in relation to total cardiovascular morbidity compared with the assessment of kidney function based on serum creatinine and eGFR.

High prevalence of early chronic kidney disease in high risk outpatients.

INTRODUCTION: Chronic kidney disease (CKD) is a significant public health problem. The aim of this study was to determine the presence of early stages of renal disease in hypertensive and diabetic outpatients without previously diagnosed renal damages. METHODS: In this cross-sectional study we studied a random sample of outpatients with essential hypertension and/or diabetes mellitus type 2 in the general practice ambulance of city Sarajevo. Renal function was evaluated by using MDRD (Modification of Diet in Renal Disease) equation and with measurement of renal biomarkers. K/DOQI classification was used to define the stages of CKD. RESULTS: The study included 200 patients, of whom 75 (37.5%) were females, mean age of 54.81 ± 6.1 years, and 125 (62.5%) male, mean age 52.46 ± 8.2 years. More than half of respondents (54.0%) were hypertensive during the follow up period. Early CKD was detected in 52% respondents. Higher prevalence of early CKD was verified in the group of patients who had hypertension associated with diabetes mellitus type 2 (59.6% vs. 47.2% in hypertension group vs. 54,0% in diabetic group, p<0.05). Significant negative correlation was found between estimated glomerular filtration rate and presence of albuminuria (p<0.001), duration of hypertension (p=0.003), duration of type 2 diabetes mellitus (p=0.021), stages of hypertension (p=0.012), female gender (p<0.001) and older age of subjects (p=0.040). CONCLUSION: Our results confirmed high prevalence of CKD and the importance of early detection of CKD in high risk groups of patients in order to prevent the progression of the same. Prevention of chronic kidney disease in our country is still not carried out satisfactorily. Required is a much greater collaboration between primary care health givers and nephrologists.

Alteration of cardiovascular structure and function in patients undergoing peritoneal dialysis.

AIMS: Cardiovascular alterations contribute to a high mortality rate in patients with end-stage renal disease (ESRD). The aims of the present study are to evaluate left ventricular (LV) function and common carotid artery (CCA) parameters and to determine risk factors associated with these changes in patients undergoing peritoneal dialysis (PD). METHODS: This longitudinal prospective study was conducted in 50 ESRD patients in whom PD had been initiated and who were observed for 18 months after the commencement of dialysis treatment, with echocardiography and CCA ultrasound parameter evaluation. RESULTS: LV hypertrophy was observed in 78% of patients at baseline and in 60% after 18 months of PD treatment. LV systolic and diastolic function was found to be significantly better after 18 months of PD treatment. Examining predictors of LV systolic function, it was found that total cholesterol was an independent positive predictor and endothelin-1 (ET-1) an independent negative predictor of LV systolic function after 18 months of treatment with PD (p < 0.001). Independent negative predictors of diastolic LV function were hemoglobin and type 2 diabetes mellitus, and daily collection of urine was an independent positive predictor (p < 0.001). Female gender was an independent negative predictor of CCA intima-media thickness, whereas body mass index, ET-1 and C-reactive protein were independent positive predictors (p < 0.001). CONCLUSIONS: The results suggest several novel modifiable mechanisms related to the short-term effects of dialysis that are potentially implicated in the development of uremic cardiomyopathy.

The importance of using peritoneal equlibration test for the peritoneal transport type characterization in continuous ambulatory peritoneal dialysis patients.

The aim of this study was to analyze the importance of the peritoneal equilibration test (PET) in evaluation of the peritoneal membrane transport status in patients treated with continuous ambulatory peritoneal dialysis (CAPD). The study included 30 adult continuous ambulatory peritoneal dialysis (CAPD) patients, 16 male and 14 female, mean age 61 +/- 16.5 years with a prescription of four exchanges of 2 litres (L) per day, who underwent peritoneal equilibration test (PET). Eleven of patients were diabetics. A modified PET was performed during a 4 hours dwell using 4.25% glucose dialysis solution. The dialysate/ plasma ratio of creatinine (D/P) at the end of the procedure, and the dialysate 240 min/ initial dialysate ratio of glucose (D/Do) were calculated and used as parameter of solute transport. With the test, categorization of patients was possible into high (H), high-average (HA), low average (LA), and low (L) transporters. In multivariate analysis age, gender, time on dialysis, comorbid diseases, diabetes mellitus (DM), serum albumin, were considered as independent factors influencing the PET. Among 30 patients 5 (16.7%) were classified as H transporters, 6 (20%) as HA, and 19 (63.3%) as LA. There were no patients in low category. Creatinine D/P at 4 hours was not different DM and non-DM patients. There were significant differences in gender, comorbid disease, serum albumin, D4/Do glucose and volume drained in 4 hours. The high transporter group had higher proportion of man (p<0.05), higher proportion of patients with comorbid diseases, lower serum albumin concentration (p<0.001), lower D4/Do glucose (p<0.001), and lower drained volume (p<0.001). The PET was en easy, inexpensive, reliable test to assess peritoneal transport type and it also provided information about peritoneal clearance of solutes and ultrafiltration. Peritoneal transport type classification was recognized not only as aid for prescription, but also as a prognostic index.

Predictors of left ventricular remodelling in kidney transplant recipents in the first posttransplant year.

Cardiovascular diseases (CVD) are a major cause of morbidity and leading cause of mortality in almost 50% of patients (pts) with chronic kidney disease (CKD), including kidney transplant recipients. Left ventricular hypertrophy (LVH) is the most common structural alteration and powerful risk factor for cardiovascular complications in the uremic patients. The aim of this study is to analyze predictors of the left ventricular remodelling in the first year after kidney transplantation based on comparison of echocardiographic findings, which had been done before and twelve months after transplantation. In five years retrospective study, we followed up 30 kidney transplant patients in the first post-transplant year. All patients data - blood pressure, BMI, ECG, blood haemoglobin, serum protein, calcium, phosphorus, product of calcium and phosphorus, the values of parathyroid hormone, serum creatinine and creatinine clearance were recorded just before kidney transplantation and in one month interval after transplantation in the first post-transplant year. Echocardiographic examination was done before transplantation and one year after kidney transplantation. Before transplantation, 33% of patients had normal echocardiographic finding and 67% of patients had echocardiographic signs of left ventricular hypertrophy. After first post-transplant year, 63% of patients showed normal echocardiographic finding of LV, while 37% of patients remained with LV hypertrophy. Diastolic dysfunction of LV until the end of study had been reduced in 40% of pts compared to 70% pts at the beginning of the study. The positive echocardiographic remodelling of LV significantly correlated with rising values of haemoglobin (p<0.05), creatinine clearance (p=0.039) and with the reduction of the serum creatinine values (p=0.047), as well as values of parathyroid hormone (p=0.022). These results confirmed positive relationship between echocardiographic remodelling of left ventricular hypertrophy and elimination uraemia-related risk factors after successful renal transplantation.

Long-term outcome of patients with lupus nephritis: a single center experience.

Lupus nephritis (LN) is an immune inflammation of kidneys caused by systemic lupus erythematosus (SLE), a chronic inflammatory disease that affects the body's immune system. Aim of this study was to analyze clinical manifestation and treatment results of patients with LN. Forty one patients with clinical signs of LN were included in the study. Mean age of patients was 31.9+/-12.1 years in the moment of first diagnosis of LN, with female-male ratio 8:1. Renal disease was pathohistologically (PTH) verified in 53.7% of patients (4 pts with class III, 17 pts with class IV, one pt with class V of lupus nephrites). Patients with high nephrotic proteinuria were treated with pulse dose of methylprednisolone and pulse doses of cyclophosphamide (CYC) in induction therapy. Corticosteroid and CYC were continued according to treatment protocol. The other group of LN patients with lower nephrotic proteinuria was treated with mycophenolate mofetil (MMF) in induction therapy at a dose of 2x1 g/day for six months, and than in maintenance 2x0.5 g/day. The patients with non-nephrotic proteinuria and normal renal function were treated with oral prednisolone 0.75-1 mg/kg/day in a single morning dose, and then gradually reduced to the dose of maintenance. The mean time of patient's follow-up was 10.9+/-4.1 years. Partial renal remission was accomplished in 29.2% pts, and complete remission in 60.9% pts for period of 17.2+/-13.3 months from the beginning of the treatment. Duration of complete renal remission was 30.1+/-19.1 months. During the period of follow-up, 29.3% pts developed at least one nephritic flare and were treated again. These results confirmed that the aggressive form of lupus nephritis should be treated associating cyclophosphamide with corticosteroids therapeutical regiment. MMF is a new promising immunosuppressive drug for a treatment of this serious disease.

The influence of risk factors in remodelling carotid arteries in patients undergoing peritoneal dialysis.

Accelerated atherosclerosis and vascular calcification, with oxidative stress, endothelial dysfunction, and other factors causing the arterial stiffness, increases cardiovascular morbidity and mortality in patients on peritoneal dialysis. The aim of this paper is to assess changes in intima media thickness (IMT) at common carotid arteries (CCA) in patients with stable continuous ambulatory peritoneal dialysis (PD) and examine the relationship of these changes and other risk factors on the occurrence of atherosclerosis. The study was conducted on 35 stable PD patients (25 type 2 diabetic patients), aged 58.6 +/- 10.6 years. CCA-IMT was assessed using ultrasound B-mode technique, bilaterally. Other risk factors for the occurrence of atherosclerosis were monitored through regular laboratory control. One atheromatous plaque was found in 19 patients (54.3%). Among 25 type 2 diabetic patients, vascular calcifications were found in 80% patients. In all PD patients, CCA-IMT is 0.77 +/- 0.23, in PD patients with vascular calcifications CCA-IMT is 1.05 +/- 0.2 mm, while in group without vascular calcifications the value of this parameter is 0.56 +/- 0.09 (p<0.01 ). Significant differences were found between PD patients with and without vascular calcifications on CCA in patients age (p<0.001), as well as values of systolic blood pressure (p=0.001), serum phosphorus (p=0.017), product calcium and phosphorus (p=0.021), CRP (p=0.039), triglycerides (p<0.05) and lipoprotein (a) values (p=0.044). Our results suggest an important determination of common carotid arteries intima media thickness and its relation to other risk factors for the occurrence and progression of atherosclerosis in patients undergoing peritoneal dialysis.

[Immunosuppressive treatment of idiopathic membranous glomerulonephritis with nephrotic syndrome]. / Imunosupresivni tretman idiopatskog membranoznog glomerulonefritisa sa nefrotskim sindromom.

AIM: The effects of two immunosuppressive therapeutic protocols have been analyzed to evaluate the influence of treatments on the level of proteinuria, value of creatinine clearance and the level of serum albumin of patients with idiopathic membranous glomerulonephritis (IMGN) and nephrotic syndrome. PATIENTS AND METHODS: We studied 30 patients with IMGN and NS. In one group, patients were treated with corticosteroids in dose of 1 mg/kg of body weight for 4 weeks, followed by gradual reduction of dose to 0.5 mg/kg, in combination with one monthly pulses of cyclophosphamide i.v. in dose of 10 mg/kg for six months, followed by pulses treatment in three months intervals. In second group cyclosporine therapy was used in dose of 3-5 mg/kg, maintaining the medication serum level at 120 +/- 20 ng/ml. The research encompassed time period from 2000 to the end of 2007, while the parameters were tested every 2 months up to 24 months in total. RESULTS: The obtained results showed that a significant reduction of proteinuria (p < 0.05) was reached in both analysed groups during the period from 6 to 9 months from the beginning of therapy. The preservation of the stabile status of the kidney function was attained as well as the insignificant variation in serum creatinine, before and after the therapy in both analysed groups. Decrease in average serum creatinine values in cyclophosphamide group (from 133.9 to 115.5 micromol/l) and the increase in the cyclosporine group (from 85.0 to 100.3 micromol/l) point to somewhat better preservation of kidney function in the cyclophosphamide group. Complete remission of nephrotic syndrome was achieved in 40% of the patients in the cyclophosphamide group, while 60% achieved partial remission. In 27% of the cyclosporine group patients complete remission was achieved, in 60% partial remission, while in 13% of them decrease of proteinuria without remission of the nephrotic syndrome. CONCLUSION: The cyclophosphamide therapy, in combination with steroids, proved to be a good choice, whereas the cyclosporine therapy proved as a prosperous alternative in treatment of patients with IMGN.

Treatment of IgA nephropathy of adults presented by nephrotic syndrome.

The aim of this retrospective study was to evaluate the results of the immunosuppressive regiment in managing of IgA nephropathy associated with primary nephrotic syndrome at the Nephrology Clinic, University of Sarajevo Clinics Centre in period of 1997-2007. We studied 19 patients (4 women and 15 men) with idiopathic nephrotic syndrome, where pathomorphologic changes of IgA nephropathy were proved by kidney biopsy. The levels of diuresis, proteinuria, albuminemia, lipidemia and kidney function, as measure of efficiency of used therapy, were monitored. The IgA nephropathy present with the nephrotic syndrome was shown in 15.8% (19) patients underwent renal biopsy due to primary nephrotic syndrome in the period of observation. The average age of patients with IgA nephropathy was 34.9+/-14.1 years. Eight patients from this group were treated with corticosteroid therapy (1-1.5 mg/kg of body weight for 4 weeks, followed by 0.5 mg/ kg of body weight until therapeutic response was achieved, and finally gradual exclusion of therapy after eight weeks in responsive patients), 6 patients with corticosteroids and bolus cyclophosphamide (10-15 mg/kg BW), and in 5/19 patients cyclosporine therapy was used (3 mg/kg BW). Complete remission of nephrotic syndrome was achieved in 42.1% of the patients. In conclusion, in adults patients with primary nephrotic syndrome associated with IgA nephropathy, used immunosuppressive therapy resulted in a high percentage of achieved remissions.

[Neuropsychiatric lupus and lupus nephritis as a clinical manifestations of systemic lupus erythematosus]. / Neuropsihijatrijski lupus i lupus nephritis kao klinicke manifestacije lupus erythematosus systemicus-a.

Neuropsychiatric (NP) lupus and lupus nephritis are one of the most profound manifestations of the Systemic lupus erythematosus (SLE), with wide variety of clinical manifestations. Especially NP lupus is the most poorly understood subset of the disease, and the most difficult therapeutic problem. We present case report of female SLE patient with the associated difficult and different clinical manifestations of central and peripheral nervous system disease end renal involvement. Agressive treatment option with intermittent pulsed intravenous cyclophosphamide and corticosteroids after the second month of treatment brought to complete remission of nephrotic syndrome. Improving of life-threating clinical manifestations of NP lupus was obtained after six months treatment by this immunosupressive therapy and included intravenous immunoglobulin 400 mg/kg body weight during five days monthly.