M. Romanowski

Experience With Autosomal Dominant Polycystic Kidney Disease in Patients Before and After Renal Transplantation : A 7-Year Observation

OBJECTIVE Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the presence of multiple cysts in both kidneys. Symptoms of the disease may arise either from the presence of cysts or from increasing loss of kidney function. First symptoms usually appear in the third decade of life: lumbar pain, urinary tract infections, arterial hypertension, or renal colic due to cyst rupture or coexistent nephrolithiasis. An early diagnosis, male gender, large kidneys by sonography, arterial hypertension, hematuria, and urinary tract infections are predictive factors of a faster progression of the disease. Our aim was to establish the indications for nephrectomy among symptomatic ADPKD patients before kidney transplantation and to assess the risks of posttransplantation complications among ADPKD patients without nephrectomy. PATIENTS AND METHODS The observed group consisted of 183 patients with ADPKD among whom 50 (27.3%) underwent kidney transplantation during a 7-year observation period (2000-2007). Among those subjects were 3 groups: (I) nephrectomy preceding transplantation; (II) nephrectomy during kidney transplantation; and (III) without nephrectomy. RESULTS Among group I before transplantation we observed: arterial hemorrhage, wound infections, and splenectomy 4 weeks after ADPKD nephrectomy; afterward we observed: urinary tract infections and contralateral cyst infection. Among group II we only observed 1 case of wound infection. Among group III we observed: ascending urinary tract infections, cyst infections, and cyst hemorrhage. Cyst hemorrhage and cyst infections led mainly to ADPKD kidney nephrectomy. During the observation time, 80.95% of grafts were functioning. CONCLUSIONS Unilateral nephrectomy is a well-founded preliminary surgical treatment before kidney transplantation. Bilateral nephrectomy before or during transplantation eliminates ADPKD complications and does not significantly increase general complications. The greatest numbers of complications and of graft losses were observed among the group without pretransplantation nephrectomy.

Activity of CuZn-superoxide dismutase, catalase and glutathione peroxidase in erythrocytes in kidney allografts during reperfusion in patients with and without delayed graft function.

Abstract:  Background:  Generation of reactive oxygen species (ROS) is the main mechanism involved in the ischemic/reperfusion damage of the transplanted organ. Oxygen burst is a trigger for complex biochemical events leading to generation of oxygenated lipids and changes in microcirculation. Many markers have been researched to prove the presence of ROS in the transplanted tissue. Some of them, like superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) are considered to play a major role in graft protection against oxygen stress during reperfusion.

Factors that impact on immediate graft function in patients after renal transplantation.

Kidney transplantation has become therapy of choice for patients with end-stage renal failure. However, many factors may cause graft rejection or delayed graft function, both of which decrease the prognosis for graft survival. For transplantologists the most important endeavor is to eliminate factors responsible for shortening graft function and to find those predictive of immediate graft function. The aim of the study was to investigate which factors influence early graft function. We retrospectively reviewed 442 renal transplant patients performed between 1990 and 1995 in two Szezecin units. All patients received an identical immunosuppressive drug schedule. Three hundred twelve patients who displayed immediate graft function were included in the study group to analyze donor and recipient age and sex, etiology of ESRD, HLA compatibility AB0 and Rh compatibility cold ischemia time, warm ischemia time, antileukocytes antibodies (PRA), and period of dialysis therapy before transplantation. We observed statistical significance for HLA and AB0 compatibility, younger donor age, and shorter cold ischemia time as the most important factors predictive of early graft function and an improved prognosis for graft survival.

Minimally Invasive Methods for the Treatment of Lymphocele After Kidney Transplantation

BACKGROUND One common complication after kidney transplantation is a lymphocele. The aim of our work was an analysis of incidence of lymphocele and the effectiveness of minimal invasive methods in the management of this complication. MATERIALS AND METHODS The examined group was consisted of 158 patients (68 female and 90 male) with end-stage renal disease who underwent kidney transplantation. RESULTS Twenty-one patients (13%) developed symptoms of lymphocele after transplantation procedure within an average time of 34 weeks. The clinical symptoms included a decrease in 24-hour urine collection, an increase in plasma creatinine concentration, abdominal discomfort, lymphorrhea with a surgical wound dehiscence, voiding problems of urgency or vesical tenesmus, febrile states, or symptoms of deep vein thrombosis. The following methods were applied with variable efficacy: aspiration with recurrence 75%; percutaneous drainage with 55%, effectiveness; laparoscopic fenestration with 72% satisfactory outcomes (1 patient presented an excessive bleeding after the procedure), and classic surgery with favorable results. CONCLUSION Percutaneous drainage guided by ultrasonic imaging should be recommended as the first attempt to cure a lymphocele. Laparoscopy is a feasible, safe technique that should be used after unsuccessful percutaneous drainage. A larger series of patients is required to confirm the superiority of minimal invasive methods to the classical approach.

Histopathologic evaluation of pretransplantation biopsy as a factor influencing graft function after kidney transplantation in 3-year observation.

BACKGROUND Many factors affect long-term results in kidney transplantation including histologic damage as a independent predictor, eg, chronic allograft dysfunction (CAD) in protocol biopsies and age-dependent lesions. Histopathologic findings correlate with the incidence of delayed graft function, eventual renal function, and allograft survival, allowing a rather precise prediction of graft outcomes. PATIENTS AND METHODS We analyzed 92 thick-needle preimplantation renal biopsies and 29 from grafts after explantation. They had been preserved in 4% formalin and immersed in paraffin. Evaluable specimens contained ≥10 glomeruli and ≥2 arterial cross-sections. We analyzed tubulitis, intensity of acute tubular necrosis (ATN), inflammatory infiltration, glomerulonephritis, arterial hyalinization, arteritis, fibrosis, tubular atrophy, arterial intimal fibrosis, increased mesangial matrix, and glomerulosclerosis percentage, although for comparative analysis not only optimal ones were taken into consideration. Over postoperative time, we analyzed patient condition, urine output, serum concentrations of creatinine, urea, uric acid, and ions as well as necessity for postoperative dialysis, ie, delayed graft function (DGF). During the 3-year observation we analyzed living recipients, graft loss, death with a functioning graft, incidence of dysfunction (CAD), and acute rejection episodes (ARE). RESULTS We observed significant correlations between immediate graft function (IGF) and lack of ATN in the pretransplantation biopsy. The presence of ATN significantly correlated with DGF and primary graft non-function. There was no correlation between renal function and arterial hyalinization or fibrosis, inflammatory infiltration, and tubular atrophy. Over postoperative time we observed significant correlations between IGF and the lack of interstitial fibrosis as well as significantly lower levels of creatinine, urea, and potassium as well as greater urine output early after transplantation. IGF correlated with shorter time to reach a creatinine level of 2 mg/dL, lower concentrations of creatinine, urea, and potassium, as well as greater diuresis during the first 5 days. In addition, lower creatinine and urea concentrations after 1 month and of urea at 6 and 36 months were associated with IGF. Female recipients showed lower concentration of creatinine over 3 months, of urea during the 1st day, and of potassium at 1 month; however, thereafter the differences were not significant. Better function of the right kidney was observed. The presence of severe ATN (ATN III) correlated with lower creatinine concentrations at 6 months and urea after 3 years. The presence of hyalinization in biopsies correlated with higher concentrations of urea at 1 year and of borderline significance after 3 years; surprisingly, potassium concentrations were lower after 2 and 3 years. The presence of inflammatory infiltrates correlated with higher creatinine concentrations after 1 and 3 years; similar correlations, albeit of borderline significance, were observed in tubular atrophy. Interstitial fibrosis correlated with creatinine concentrations during 10 days after the operation and after 12 months, also with potassium concentrations 5 days after the operation. Borderline correlations were observed between donor age and creatinine concentration in the first day after the operation, after 6 months, and time to achieve a creatinine concentration of 2 mg/dL. We observed that biopsies with greater numbers of glomeruli correlated with better graft function, namely, lower creatinine concentrations after 5 days as well as at 1 and 6 months, as well as lower urea concentrations after 5 days and 6 months. We also observed differences in renal function depending on gender. The presence of acute tubular necrosis, arterial fibrosis and a lack of inflammatory infiltration in pretransplantation biopsy correlated with worse late renal function. Explantation biopsies showed signs of CAD in 66.4% and histologic features of ARE in 38.51%.

The impact of CTLA4 and PTPN22 genes polymorphisms on long-term renal allograft function and transplant outcomes

Abstract Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) downregulates the immune system. Lymphoid tyrosine phosphatase (Lyp)—PTPN22 protein—is suggested to be negative regulator of T-cell reaction. There are several polymorphisms in the CTLA4 and PTPN22 genes, which can influence the immune response and allograft function after kidney transplantation. The aim of this study was to examine the impact of CTLA4 and PTPN22 genes polymorphisms on the long-term renal transplant function and recipients’ outcomes during a 5-year follow-up observation. The study enrolled 268 Caucasian renal transplant recipients. Genotyping of the rs231775 (+49AG) CTLA4 gene polymorphism was performed using real-time PCR and rs2476601 (C1858T) PTPN22 gene polymorphism using PCR-RFLP method. The 5-year graft survival rate was 81.7%. Dialysis was necessary in 22 (8%) patients, 7 (2.6%) patients died and 20 (7.4%) switched to another transplantation center. We found no association between studied polymorphisms and graft loss/dialysis. Comparison of the distribution of the +49AG CTLA4 and C1858T PTPN22 genes polymorphisms genotypes among dead and living patients showed no statistically significant differences. Above results suggest that the rs231775 (+49AG) CTLA4 and rs2476601 (C1858T) PTPN22 genes polymorphisms are not associated with long-term allograft failure, graft loss and mortality after transplantation.

Adiponectin and leptin gene polymorphisms in patients with post-transplant diabetes mellitus.

BACKGROUND Post-transplant diabetes mellitus (PTDM) is a common metabolic complication after organ transplantation and may be associated with the use of calcineurin inhibitors (tacrolimus and cyclosporine). Leptin and adiponectin are adipokines and play an important role in the regulation of insulin secretion as well as glucose and lipid metabolism. AIM The aim of this study was to examine the association between adiponectin and leptin gene polymorphisms and development of PTDM. MATERIALS & METHODS The study included 323 patients who received kidney transplants and were treated with calcineurin inhibitors (tacrolimus or cyclosporine). RESULTS The association between adiponectin and leptin gene polymorphisms and PTDM was studied in three models of Cox regression analysis--additive, dominant and recessive. In these three models, the LEP rs2167270 gene polymorphism was statistically significantly associated with increased risk of PTDM. The association between the LEP rs2167270 polymorphism and PTDM was confirmed by multivariate regression analysis. CONCLUSION The results of our study suggest an association between the leptin rs2167270 gene A allele and PTDM. Original submitted 27 February 2015; Revision submitted 22 May 2015.

Impact of selected factors on early graft function in patients after renal transplantation

Transplantation is the best treatment for end-stage renal diseases. For transplantologists, it is most important to know the factors that worsen graft survival prognosis. The aim of the study was to investigate factors predictive of graft loss and shortened graft survival. We retrospectively reviewed 442 renal transplant patients between 1990 and 1995 in two Szczecin units, all of whom received a triple-drug immunosuppressive regimen. One hundred thirty patients showed graft disorders such as delayed graft function or primary nonfunction. The occurrence of these disorders was examined as a function of donor and recipient age and sex, cause of ESRD, HLA compatibility, ABO and Rh compatibility, cold ischemia time, warm ischemia time, antileukocyte antibody level (PRA), and period of dialysis therapy before transplantation. The study showed that a high maximal PRA level, incompatibility for ABO group, and a longer warm ischemia time increase the probability of early graft function disorders.

Urinary Metalloproteinases-9 and -2 and Their Inhibitors TIMP-1 and TIMP-2 are Markers of Early and Long-Term Graft Function After Renal Transplantation.

Background/Aims: Renal ischemia-reperfusion (I-R) injury (IRI) is an inseparable feature of organ transplantation and may have a negative impact on the graft, its function and survival. Acute tubular necrosis, which is reversible thanks to the regenerative capacity of renal tubular epithelial cells, is the main cause of acute renal failure secondary to IRI. MMP-2 and MMP-9 are proteolytic enzymes involved in digesting proteins that are components of the extracellular matrix (ECM) and the basement membrane of the nephrons. This way post-reperfusion MMP activation allows the inflammatory process to spread. Methods: In our studies, we focused on identifying whether the concentrations of MMP-2 and MMP-9 and their natural inhibitors TIMP-1 and TIMP-2 in urine sample at day 1 and day 30 as well as after 12 months following renal transplantation are markers of early and long-term renal function during meanly five-years observation. Moreover, in urine sampled at months 6 and 12 after renal transplantation, we determined the content of TGF-β as a graft fibrosis indicator. Results: MMP-9 concentration in the early post-transplant period is a major marker of early and long-term function of the transplanted kidney. Its increased concentration was correlated with lesions related to tubular atrophy and fibrosis in renal biopsies performed at months 3 and 12 after transplantation. Its concentration is correlated with TGF-β content in a later period. Conclusions: TIMP-1 and-2 are primarily markers of an early function of the transplanted kidney. Early post-transplant concentration of MMP-2 is a marker of proteinuria in early and long-term post-transplant periods.

Early phase of reperfusion of human kidney allograft does not affect an erythrocyte anti‐oxidative system

Background:  Generation of reactive oxygen specimens is the basic mechanism leading to ischaemia/reperfusion injury of the kidney graft. Oxygen burst is a trigger for sophisticated biochemical changes leading to generation of oxygenated lipids and changes in microcirculation, which recruit recipient’s neutrophils and contribute to delayed graft function. It has been shown that the free radicals generation correlates with the activity of anti‐oxidative system. Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione (GSH) are involved in protection against free radicals.