Mycophenolate mofetil combined with steroids: New experiences in the treatment of idiopathic retroperitoneal fibrosis

Background/Aim. Idiopathic retroperitoneal fibrosis (IRF) is an uncommon disease characterized by a retroperitoneal fibrotic tissue that often involve the ureters, leading to the obstructive nephropathy and variable impairment of renal function. Findings strongly suggest an autoimmune etiology. Surgery, medical treatment with immunosuppressive drugs, or a combination of both are proposed. The optimal treatment has not been established yet. The aim of this study was to present our experience with combined immunosuppressive therapy of IRF, steroids (S) and mycophenolate mofetil (MMF). Methods. We prospectively followed four patients with IRF from January 2004 to December 2006. Three patients had an active disease with bilateral hydronephrosis. In the two of them acute renal failure was presented, and ureteral catheters were inserted in one in order to manage ureteral obstruction. One patient has came to our unit with a relapse of IRF and incipient chronic renal failure after the prior therapy with ureterolysis and immunosuppressive drugs (azathioprine and tamoxifen). All patients received steroids and MMF. Two patients were treated with intravenous methylprednisolone pulses (250 mg each), for three consecutive days, followed by oral prednisone 0.5 mg/kg/day. The other two patients received oral prednisone at the same dose. Prednisone was gradually tappered to a maintenance dose of 10 mg/kg/day. Simultaneously, all patients received MMF, initially 1 g/day with the increase to 2 g/day. Results. After four weeks of the therapy all symptoms disappeared, as well as a hydronephrosis with a decrease of erythrocyte sedimentation rate and Creactive protein (CRP) to normal level in all patients. Three patients remain in remission untill the end of the follow up. One patient had a relapse because of stopping taking the therapy after six months. He was treated by oral prednisone 0.5 mg/kg/day, which was gradually decreased. After twelve weeks hydronephrosis disappeared and CRP returns to the normal level. Conclusion. The combination of steroids and mycophenolate mofetil led to the remission of IRF with a strong and quick immunosuppressive effect. It also provided avoiding the long-term use of high steroid dose and surgical procedures.

Angiotensin II type 1 receptor gene polymorphism could influence renoprotective response to losartan treatment in type 1 diabetic patients with high urinary albumin excretion rate

Background/Aim. Diabetic nephropathy (DN) is a clinical syndrome characterized by persistent albuminuria, increasing arterial blood pressure and progressive decline in glomerular filtration rate (GFR). When persistent albuminuria is established, antihypertensive treatment becomes most important factor in slowing the progression of diabetic glomerulopathy. The aim of this study was to examine if renoprotective response to a short-term losartan therapy depends on 1166 A/C gene polymorphism for its target receptor. Method. The study included 35 patients with diabetes mellitus type 1 and persistently high urinary albumin excretion rate (UAE: > 30 mg/24 h), genotyped for the 1166 A/C gene polymorphism for the angiotensin II type 1 receptor (AT1R). The participants were segregated into 3 genotype groups according to combinations of A or C allele: AA(16%), AC(15%) and CC(11%). The patients received losartan 50 mg daily for 4 weeks, following 100 mg daily for another 8 weeks. At baseline and after 12 weeks of the treatment period UAE, blood pressure, GFR and filtration fraction (FF) were determined. Results. After 12 weeks of the treatment with losartan, albuminuria was reduced from baseline by 9% [95% confidence interval (CI): 1-17, p = 0.039] in the AA genotype, and by 11% (95% CI: 6-17, p = 0.0001) in the AC genotype. Losartan treatment reduced albuminuria in the CC group by 5% (95%CI: -13-22, p = 0.47). Glomerular filtration rate remained unchanged in all genotype groups. Filtration fraction was significantly reduced from baseline by 0.018 ± 0.024 (p = 0.012) only in the AC genotype. In the AA genotype, FF was reduced from baseline by 0.017 ± 0.03 (p = 0.052), and in the CC genotype by 0.01 ± 0.008 (p = 0.092). In the AA group, systolic blood pressure declined from 136 ± 24 mmHg at baseline, to an average of 121 ± 18 mmHg at the end of the study (p = 0.001). The AC group achived reduction from 131 ± 10 mmHg at baseline to 115 ± 7 mmHg (p = 0.001) during the investigation period. In the AA genotype group losartan reduced diastolic blood pressure from 86 ± 13 mmHg at baseline to 78 ± 8 mmHg (p = 0.004), and in the AC genotype from 88 ± 5 mmHg at baseline to 11.7 ± 5.6 mmHg during the investigation period (p = 0.001). In the CC genotype diastolic blood pressure reduction remained nonsignificant (p = 0.066). Conclusion. The results of our small sample size study provide the evidence that 1166 A/C AT1R polymorphism could be associated with the renoprotective response to losartan therapy

Conversion from calcineurin inhibitors to sirolimus of recipients with chronic kidney graft disease grade iii for a period 2003-2011

Background/Aim. Tremendous breakthrough in solid organ transplantation was made with the introduction of calcineurin inhibitors (CNI). At the same time, they are potentially nephrotoxic drugs with influence on onset and progression of renal graft failure. The aim of this study was to evaluate the outcome of a conversion from CNIbased immunosuppressive protocol to sirolimus (SRL) in recipients with graft in chronic kidney disease (CKD) grade III and proteinuria below 500 mg/day. Methods. In the period 2003-2011 24 patients (6 famale and 18 male), mean age 41 ± 12.2 years, on triple immunosuppressive therapy: steroids, antiproliferative drug [mycophenolate mofetil (MMF) or azathiopirine (AZA)] and CNI were switched from CNI to SRL and followe-up for 76 ± 13 months. Nine patients (the group I) had early postransplant conversion after 4 ± 3 months and 15 patients (the group II) late conversion after 46 ± 29 months. During the regular outpatient controls we followed graft function through the serum creatinine and glomerular filtration rate (GFR), proteinuria, lipidemia and side effects. Results. Thirty days after conversion, in all the patients GFR, proteinuria and lipidemia were insignificantly increased. In the first two post-conversion months all the patients had at least one urinary or respiratory infection, and 10 patients reactivated cytomegalovirus (CMV) infection or disease, and they were successfully treated with standard therapy. After 21 ± 11 months 15 patients from both groups discontinued SRL therapy due to reconversion to CNI (10 patients) and double immunosuppressive therapy (3 patients), return to hemodialysis (1 patient) and death (1 patient). Nine patients were still on SRL therapy. By the end of the follow-up they significantly improved GFR (from 53.2 ± 12.7 to 69 ± 15 mL/min), while the increase in proteinuria (from 265 ± 239 to 530.6 ± 416.7 mg/day) and lipidemia (cholesterol from 4.71 ± 0.98 to 5.61 ± 1.6 mmol/L and triglycerides from 2.04 ± 1.18 to 2.1 ± 0.72 mmol/L) were not significant. They were stable during the whole follow-up period. Ten patients were reconverted from SRL to CNI due to the abrupt increase of proteinuria (from 298 ± 232 to 1639 ± 1641/mg day in 7 patients), rapid growth of multiple ovarian cysts (2 patients) and operative treatment of persisted hematoma (1 patient). Thirty days after reconversion they were stable with an insignificant decrease in GFR (from 56.10 ± 28.09 to 47 ± 21 mL/min) and significantly improved proteinuria (from 1639 ± 1641 to 529 ± 688 mg/day). By the end of the follow-up these patients showed nonsignificant increase in the serum creatinine (from 172 ± 88 to 202 ± 91 mmol/L), decrease in GFR (from 56.10 ± 28.09 to 47 ± 21 mL/day) and increased proteinuria (from 528.9 ± 688 to 850 ± 1083 mg/min). Conclusion. In this small descriptive study, conversion from CNI to SRL was followed by an increased incidence of infections and consecutive 25-50% dose reduction in the second antiproliferative agent (AZA, MMF), with a possible influence on the development of glomerulopathy in some patients, which was the major reason for discontinuation of SRL therapy in the 7 (29%) patients. Nine (37.5%) of the patients experienced the greatest benefit of CIN to SRL conversion without serious post-conversion complications

Nephronophthisis and medullary cystic kidney disease complex

Background. Nephronophthisis and medullary cystic kidney disease complex refers to the genetic heterogeneous group of inherited tubulointerstital nephritis. Nephronophthisis comprises at last 3 clinical manifestations, has the autosomal recessive pattern of inheritance, appears early in life and is the most frequent inherited kidney disease that causes terminal renal failure in childhood, while medullary cystic kidney disease has the autosomal dominant pattern of inheritance, is less frequent, and terminal renal failure appears later in life. These two forms have similar clinical and morphological findings but extrarenal manifestations, the median ages of occurrence of terminal renal failure, and siblings presence help us distinguish these diseases. Case report. In this article we illustrated the case of a 20- years old patient with the suspicion of having complex nephornophthisis and medullary cystic kidney disease based upon mild renal failure, seen in routinely taken laboratory findings and bilateral cysts in corticomedullary region of the kidneys verified on abdominal ultrasound examination. Conclusion. This disease should rise suspicion in children or adolescents with progressive renal failure, a typical clinical manifestation, blood and urine samples results, bilateral cysts in the corticomedullary region of the kidneys seen during ultrasound examination of the kidneys and family inheritance

Asymptomatic renal damages in persons with chronic professional exposure to elementary mercury low concentrations

Background/Aim. Any forms of mercury have toxic action on the majority of organs, especially kidneys. The major source of professional exposure to mercury are departments for the production of chlorine which use mercury as catode. The aim of the study was to prove that chronic exposure to elementary mercury low concentrations could cause asymptomatic damages of the kidneys. Methods. A total of 40 workers from the factory "HIP Petrohemija" Pančevo, of the mean age 45±8 years, who were exposed to the effects of mercury for more than 20 years within the production procedure, and 20 workers from the factory "Panonijaplast" Pančevo, of the mean age 44±7 years, who were not exposed to mercury nor to other nephrotoxic agents, were submitted to laboratory analysis, renal function testing, and determination of mercury concentration in urine. Mercury concentration was also measured in the air of working premises of the factory. Results. The performed measurements confirmed that the concentrations of mercury at any tested working place in the Department of Electrolysis were not more than the maximally permitted concentration for an 8-hour exposition. In the exposed group (40 examinees) 75% of the examinees had mercury in urine in the concentration < 0.1 μmol/l, while in 25% of them it was 0.1-0.75 μmol/l. In the control group (20 examinees) all of the examinees showed to have < 0.1 mol/l mercury in urine. There was determined a positive corelation between the concentration of mercury in urine and the value of β2-microglobulin (p < 0.05), as well as between the corrcentration of mercury in urine and γGT activity (p < 0.05), and between the concentration of mercury in urine and the value of retinol-binding protein (p < 0.01). Conclusion. In 25% of the examinees excretion of mercury was significantly higher than in the control group. The frequency of asymptomatic renal tubular lesions and dysfunction of moderate extent were found to be higher in the exposed group than in the control one

Efficacy of valsartan in the therapy of persistent microalbuminuria in normotensive patients with type 1 diabetes mellitus

Aim. To determine the efficacy of AT1 receptor antagonist (valsartan) in decreasing of urinary excretion of albumin in normotensive patients with type 1 diabetes and incipient diabetic nephropathy (DN). Methods. This was a prospective, randomised, placebo-controlled study, which included 20 patients with insulin-dependent diabetes mellitus, mean age 25.15, and the duration of diabetes of 13.95 years. All the patients were normotensive, with persistent microalbuminuria (incipient phase of DN). Patients were randomly divided into two groups (10 patients each): valsartan group treated with 80 mg valsartan daily during 6 months, and the group treated with placebo during the same period. Both groups were similar and comparable concerning the observed parameters at the beginning of the study. Results. After 6 months therapy, valsartan caused significant decrease of urinary albumin excretion rate (UEAR) by 69.1% from 64.8 to 21.1 mg/24 h, while in placebo group there was an insignificant increase of UEAR by 29.8%. During the follow-up of UEA in the observed groups, at the beginning and the end of the mentioned period highly significant decrease of albumine secretion (p<0.001) was observed. Valsartan significantly lowered mean systolic blood pressure (from 122.0 ± 10.1 to 110.0 ± 11.8 mmHg). After 6 months therapy, the reduced values of total cholesterol and LDL-cholesterol fraction were registered in the valsartan group, while the difference in serum trigliceride values reached statistical significance (1.42 ± 0.79 vs. 1.21 ± 0.89 mmol/L; p<0.05). Neither significant difference in glycoregulation quality between the two groups, nor the occurence of hyperkalemia was detected throughout the study period. Conclusion. Valsartan's efficacy in the decrease of microalbuminuria after 6 months of therapy could justify the use of this group of renin/angiotensin blockers in delaying the clinically manifested DN. Valsartan was well tolerated and did not influence the quality of glycoregulation. It did not increase the level of serum lipids and could be recomended in the treatment of diabetic patients

Comparative analysis of the efficacy and biocompatibility of various methods of dialysis

Background/Aim. The efficacy and biocompatibility of hemodialysis have a singnificant impact on dialysis patient morbidity and mortality rate. The aim of our study was to compare the efficacy and biocompatibility of different hemodialysis modalities in our patients. Methods. A total of 55 patients were included in the study, and on the basis of dialysis modality, they were divided in four groups: group I - postdilution on-line hemodiafiltration (n = 15), group II - bicarbonate high-flux polysulphone hemodialysis (n = 15), group III - bicarbonate low-flux polysulphone hemodialysis (n = 15), and groupe IV - bicarbonate cuprophane hemodialysis (n = 10). The efficacy was evaluated on the basis of urea reduction rate (URR), urea Kt/V index and serum β2-microglobuline reduction rate, and the biocompatibility was evaluated on the basis of the leukocyte count fall during the first fifteen minutes of dialysis session, and of the serum C-reactive protein (CRP) level. Results. The highest mean URR was achieved in the group I (70.53 ± 6.49 %), and it was significantly higher in comparison with the average URR in the group IV (54.8 ± 6.35%) (p = 0.001). The average value of urea Kt/V index in the group I (1.48 ± 0.22) was significantly higher in comparison with the average value in the groupe II 1.30 ± 0.22 (p < 0.05), group III (1.05 ± 0.22), and group IV (0.98 + 0.22) (p = 0.001). Serum β2-microglobuline reduction rate was 68.93 ± 8.25% in the group I, and 58.86 ± 7.98% in the groupe II (p = 0.01). During the first 15 minutes of hemodialysis the leukocyte number was decreased by 12.57 ± 9.35% in the group I, 13.61 ± 9.64% in the group II, 18.3 ± 13.24 in the group III and 62.3 ± 15.4 in the group IV, on average. The mean serum level of CRP was 9.4 ± 6.47 mg/l in the group IV, and less than 3.5 mg/l in the group I of the patients (p = 0.001). Conclusion. Postdilution on-line hemodiafiltration in comparison with standard hemodialysis provided the more effective elimination of small and middle uremic toxins molecules and a significantly higher degree of biocompatibility. The patients treated with standard hemodialysis frequently do not achieve the minimal value of urea Kt/V index prescribed by National Kidney Foundation - Dialysis Outcomes Quality Inatiatives standards. These patients also have significantly higher serum CRP values which suggest the state of chronic microinflammation

Brown tumor of the maxilla in patient with secondary hyperparathyroidism

Brown tumor or parathyroid osteopathy is a kind of bony lesion caused by hyperparathyroidism. It appears as an expansive osteolytic lesion mostly in mandible, ribs, pelvis and femur, but rarely in the upper jaw. Bone resorption is the result of osteoclastic activity due to an increased activity of parathyroid hormone. A 25-years-old male patient was operated on due to clinicaly and radiographicaly obvious maxillary tumor and increased values of parathyroid hormon (PTH - 1 050 ng/l). The level of calcium in blood was normal (Ca 2.34 mEq/L). The patient was dialyzed for years because of the chronic renal failure. Histopathologic analysis confirmed brown tumor, that appeared as bony lesion of secondary hyperparathyroidism due to the chronic renal failure. The operation of the upper jaw had been performed before parathyroidectomy, due to an excessive growth of tumor followed by heavy epistaxes. The subsequent parathyroidectomy was followed by the regression of remaining bony lesions

Living unrelated donor kidney transplantation: A fourteen-year experience

Background. In countries without a national organization for retrieval and distribution of organs of the deceased donors, problem of organ shortage is still not resolved. In order to increase the number of kidney transplantations we started with the program of living unrelated - spousal donors. The aim of this study was to compare treatment outcome and renal graft function in patients receiving the graft from spousal and those receiving ghe graft from living related donors. Method. We retrospectively identified 14 patients who received renal allograft from spousal donors between 1996 and 2009 (group I). The control group consisted of 14 patients who got graft from related donor retrieved from the database and matched than with respect to sex, age, kidney disease, immunological and viral pretransplant status, the initial method of the end stage renal disease treatment and ABO compatibility. In the follow-up period of 41 ± 38 months we recorded immunosuppressive therapy, surgical complications, episodes of acute rejection, CMV infection and graft function, assessed by serum creatinine levels at the beginning and in the end of the follow-up period. All patients had pretransplant negative cross-match. In ABO incompatible patients pretransplant isoagglutinine titer was zero. Results. The patients with a spousal donor had worse HLA matching. There were no significant differences between the groups in surgical, infective, immunological complications and graft function. Two patients from the group I returned to hemodialysis after 82 and 22 months due to serious comorbidities. Conclusion. In spite of the worse HLA matching, graft survival and function of renal grafts from spousal donors were as good as those retrieved from related donors