J. Sieńko

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.

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.

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%.

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.

The outcomes of treatment and the etiology of lymphoceles with a focus on hemostasis in kidney recipients: a preliminary report.

BACKGROUND The etiopathogenesis of lymphoceles remains incompletely understood. The aim of our work was to analyze the perturbations of blood coagulation process for their possible impact on the etiology of lymphoceles. Additionally we performed an evaluation of the incidence and effectiveness of treatment methods for lymphoceles. MATERIALS AND METHODS During 2004 to 2010, we performed 242 kidney transplantations in 92 female and 150 male patients. The hemostatic parameters included concentrations of: antithrombin, plasminogen, thrombin/antithrombin complexes (TAT), prothrombin products F1+2 (F1+2), d-dimers, and plasmin/antiplasmin complexes. RESULTS At 7 years follow-up 27 (11%) recipients had developed symptomatic lymphoceles, namely abdominal discomfort, a palpable mess in the lower abdomen, arterial hypertension, infection of the operative site with fever, lymphorrhoea with surgical wound dehiscence, decreased diurnal urine output with an elevated plasma creatinine, voiding problems of urgency and vesical tenesmus, and/or symptoms of deep vein thrombosis. We applied the following methods of treatment aspiration alone, percutaneous drainage, laparoscopic fenestration or open surgery. In two only patients did perform open surgery. Since 2008 we have not performed an aspiration alone because of high rate of recurrence (almost 100%) and abandoned open surgery in favor of a laparoscopic approach. Our minimally invasive surgery includes percutaneous drainage guided by ultrasound and a laparoscopic procedure with 100% effectiveness. The examined hemostatic parameters revealed decreased concentrations of TAT complexes and F1+2 in subjects with lymphocele showing positive predictive values of 33% and 41% respectively. The negative predictive values for TAT complexes and F1+2 were 14% and 10%, respectively, suggesting decreased blood coagulation activity among effected recipients. Altered blood coagulation processes may explain some aspects of the disturbances of postoperative obliteration of damaged lymphatic vessels and formation of pathological lymph collection afterward. CONCLUSIONS Perturbations of blood coagulation may be one cause for a lymphocele.

Reversal to Whole-Brain Death Criteria After 15-Year Experience With Brain Stem Death Criteria in Poland

Polish brain-death criteria, similar to the original Harvard criteria, were published in 1984. In 1990, they were converted to brainstem death criteria, and were revised twice, in 1994 and in 1996. However, they could not be used in many complicated clinical situations such as intoxication, metabolic alterations, major facial injury, infratentorial lesions, and cervical spinal cord injury. The new Polish Transplant Act, passed by the Polish Parliament in 2005, recommends implementation of criteria for whole-brain death for brain-death diagnosis. In 2007, the Polish Ministry of Health Commission outlined new Polish brain-death criteria. Optional use of instrumental confirmatory tests was implemented in the new Polish national code of practice for the diagnosis of brain death in adults. In children up to age 2 years, instrumental tests are obligatory. Initially, there were problems in understanding the new, slightly more complicated classifications of primary and secondary brain injuries, infratentorial and supratentorial processes, modified apnea test. A broad commentary that addressed the most frequently asked questions was published in Anesthesiology and Intensive Therapy, the official journal of the Polish Society of Anaesthesiology and Intensive Therapy. This article dealt with most of the problems associated with implementation of the new criteria for diagnosis of brain death.

Does Calcium Channel Blocker Improvement of Perfusion Impact the Functioning of Kidney Graft in Early Period After Transplantation

The aim of the study was to evaluate the influence of reduced vascular resistance following calcium channel blocker verapamil administration on kidney function at 3 months after transplantation. A group of 48 kidneys received 100 microg verapamil by injection directly into renal artery before starting perfusion. The control group included 48 paired kidneys without verapamil addition. Calcium channel blocker therapy with verapamil greatly decreased renal vascular resistance but it did not affect graft function. Administration of calcium channel blockers improved kidney function in the early period after transplantation. A better-functioning graft seems to be based more on metabolic than hemodynamic effects.

Methylene Blue Usage in Horseshoe Kidney Graft Separation: Case Report

Definitive diagnostics and strict procedures during kidney donor qualification are required. Nowadays, precise and accurate imaging techniques are at hand for every diagnostician. However, many studies have described intraoperative occurrence of horseshoe kidney. Although the harvesting procedure in the case of horseshoe kidney is not technically difficult, graft separation for successful renal transplantation is a challenge. The complex anatomy of malformed organs causes issues during kidney separation. This procedure may lead to damage of the collecting urinary system as well as vascularization damage. Separate graft transplantation is probable when a thin isthmus in a horseshoe kidney is present. Otherwise, poor graft function may occur. We present a technique for horseshoe kidney separation with the use of methylene blue for vascularization determination. The above-mentioned procedure was performed with the methylene blue solution dose injected into a single renal graft artery. Even with the malformed organs thick isthmus, the exact incision line was identified, exposing vascular perfusion asymmetry and allowing precise renal graft separation.

Effect of Immunosuppressive Therapy on Proteinogram in Rats.

Background It has been observed that the use of immunosuppressive drugs in patients after transplantation of vascularized organs may be associated with changes in the concentration of certain fractions of plasma proteins. The concentration of these proteins was correlated with an increased risk of occurrence of stage 3 chronic kidney disease (CKD). This article examines the effect of the most commonly used immunosuppressive drugs on the concentration of plasma proteins in Wistar rats. Material/methods The study involved 36 rats grouped according to the immunosuppressive regimen used (tacrolimus, mycophenolate mofetil, cyclosporine A, rapamycin, and prednisone). The rats in all study groups were treated with a 3-drug protocol for 6 months. The treatment dose was adjusted based on available data in the literature. No drugs were administered to the control group. The rats were sacrificed and blood samples collected to determine the concentration of plasma proteins using electrophoresis technique. Results Statistically significant differences were observed between protein concentrations within the studied groups. The differences related to the proteins with masses of 195 kDa, 170 kDa, 103 kDa, and 58 kDa. Conclusions (1) Immunosuppressive drugs caused changes in the proteinogram of plasma proteins. (2) The strongest effect on rat plasma proteins was exerted by a regimen based on rapamycin. Intermediate, weak, and weakest effects were observed in regimens based on cyclosporine A, tacrolimus, and mycophenolate mofetil, respectively.

Does Immunosuppressive Therapy Affect Markers of Kidney Damage

BACKGROUND Markers currently used to detect kidney damage are effective in both early (KIM-1, NGAL) and late (MCP-1, MMP, TIMP) stages of renal tubular damage, indicating the progression of chronic kidney disease. Immunosuppressive drugs may damage the transplanted organ through their direct toxic effects and by contributing to the development of chronic fibrosis and tubular atrophy. The aim of this study was to determine if immunosuppressive drugs per se affect the concentration of kidney damage markers, by using concentrations and doses of immunosuppressive within therapeutic, not toxic, levels in rat blood. MATERIAL AND METHODS The study involved 36 rats grouped according to the immunosuppressive regimen used (tacrolimus, mycophenolate mofetil, cyclosporin A, rapamycin, and prednisone). The rats were treated with a 3-drug protocol for 6 months. No drugs were administered to the control group. The blood samples were collected to determine the concentration of kidney damage markers by using enzyme-linked immunosorbent assay (ELISA). RESULTS 1. In the groups receiving regimens based on cyclosporin A (CyA), significantly higher concentrations of KIM-1 in plasma was observed compared to cases not treated with drugs. 2. The use of tacrolimus was associated with increased concentrations of MCP-1 in plasma and rapamycin was associated with decreased concentrations of MCP-1 in plasma. 3. Rapamycin induces an unfavorable, profibrotic imbalance between metalloproteinase-9 and its inhibitor, TIMP-1. CONCLUSIONS Commonly used immunosuppressive drugs influence the concentration of blood markers of kidney damage. This fact should be taken into account when analyzing the association between the concentration of these markers and pathological processes occurring in the transplanted kidney.