Ljiljana Ignjatovic

Asymptomatic urinary abnormalities: Histopathological analysis

The aim of the study was to assess the characteristics of histopathological changes in 120 young males, both recruits and soldiers, who had undergone successful renal biopsy due to asymptomatic urinary abnormalities. The patients were subdivided into a group with isolated microhematuria (IMH-62 patients) and a group with asymptomatic microhematuria and proteinuria (MHP-58 patients). Light, immunofluorescence, and electron microscopy revealed that MHP was associated with more severe morphological changes, than IMH. The latter group included 6 subjects with normal biopsies and 13 subjects with minor abnormalities found only in two patients with MHP. The frequencies of particular nephropathies in the groups with IMH and MHP were as follows: 35% and 55% for IgA nephritis, 24% and 31% for non-IgA mesangioproliferative glomerulonephritis (GN), 2% and 3% for focal proliferative GN, 3% and 3% for diffuse proliferative GN, 5% and 1% for thin basement membrane nephropathy, respectively. Rebiopsy, performed in eight patients due to worsening of proteinuria during the follow-up period, showed evidence of progression of morphological changes. Patients with IMH had significantly less prominent histopathological changes than patients with MHP. Therefore, renal biopsy cannot be recommended for patients with IMH unless specific indications are present.

Our first experiences in applying an original method for removal of ABO-isoagglutinins in ABO-incompatible kidney recipients

BACKGROUND/AIM Due to improved methods for removal of ABO isoagglutinins and novel immunosuppressive protocols, short and long-term outcome in blood group incompatible is similar to blood group compatible kidney transplantation. The aim of this study was to determine the efficacy of our original method for removal of ABO isoagglutinins from the blood in ABO-incompatible kidney allograft recipients. METHOD Between 2006 and 2008 twelve patients were transplanted from ABO incompatible living donors. Titers of ABO isoagglutinins were 4-128 (IgG). Immunosuppressive therapy started 14 days before kidney transplantation with rituximab, followed by a triple therapy (prednisone + tacrolimus + mycophenolate mofetil) and the first plasma exchange (PE) procedure, in which one plasma volume was substituted with albumin and saline on day 7 before transplantation. For selective extracorporeal immunoadsorption, the removed plasma was mixed with donor blood type filtered red blood cells, centrifuged and the supernatant separated and preserved. In the next PE procedure, the removed plasma was replaced with immunoadsorbed plasma, and so on. Titers of ABO agglutinins, renal allograft function and survival were followed-up. RESULTS The pre-transplant treatment consisting of 1-5 PE procedures and immunosuppressive therapy resulted in target ABO agglutinins titers below 4. During a 10-24 month follow-up three patients had an early acute rejection, one patient acute rejection and hemolytic anemia, two patients surgical complications and one of them lost his graft. In the post-transplant period, the titers of ABO antibodies remained below 4. All the patients had stable kidney allograft function with mean serum creatinine +/- SD of 129 +/- 45 micromol/l at the end of the study. CONCLUSION Our method for removal of ABO antibodies was effective in a limited series of patients and short-term follow-up.

[Mycophenolate mofetil combined with steroids: new experiences in the treatment of idiopathic retroperitoneal fibrosis].

BACKGROUND/AIM [corrected] 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 patents 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.

The value of urine cytologic examination findings in the diagnosis of the acute renal allograft rejection

BACKGROUND: Acute rejection of allograft is one of the most serious complications of renal transplantation that requires fast and precise diagnostic approach. In this paper our experience in cytologic urinalysis as a diagnostic method of the acute renal allograft rejection was reviewed. METHODS: The study group included 20 of 56 patients with transplanted kidneys who were assumed for the acute allograft rejection according to allograft dysfunction and/or urine cytology findings. Histological findings confirmed allograft rejection in 4 patients. Urine sediment obtained in cytocentrifuge was air-dried and stained with May-Grunwald-Giemsa. Acute allograft rejection was suspected if in 10 fields under high magnification 15 or more lymphocytes with renal tubular cells were found. RESULTS: Acute transplant rejection occurred in 32.1% patients. In 15 patients clinical findings of the acute renal allograft rejection corresponded with cytological and histological findings (in the cases in which it was performed). Three patients with clinical signs of the acute allograft rejection were without cytological confirmation, and in 2 patients cytological findings pointed to the acute rejection, but allograft dysfunction was of different etiology (acute tubular necrosis, cyclosporine nephrotoxicity). In patients with clinical, cytological and histological findings of the acute allograft rejection urine finding consisted of 58% lymphocytes, 34% neutrophilic leucocytes and 8% monocytes/macrophages on the average. The accuracy of cytologic urinalysis related to clinical and histological finding was 75%. CONCLUSION: Urine cytology as the reliable, noninvasive, fast and simple method is appropriate as the a first diagnostic line of renal allograft dysfunction, as well as for monitoring of the graft function.

Predijalizna transplantacija bubrega

Predijalizna transplantacija bubrega je sa medicinskog i socioekonomskog aspekta metoda izbora u lecenju terminalne bubrežne insuficijencije kod bolesnika koji imaju živog davaoca bubrega. Nase pocetno iskustvo sa ovom metodom lecenja vrlo je afirmativno. Predijalizna transplantacija bubrega je posebno prihvatljiva kod dece, dijabeticara i bolesnika sa losim pristupom za dijalizu. U nasoj zemlji postoje dodatni medicinski (los kvalitet dijalize, visok rizik od infekcije virusima hepatitisa, visok rizik od senzibilizacije na tkivne antigene transfuzijama krvi) i paramedicinski razlozi (prepunjenost dijaliznih centara, ograniceni zdravstveni ekonomski resursi) koji namecu potrebu daljeg razvijanja programa predijalizne transplantacije.

Kidney failure as an unusual initial presentation of biclonal gammopathy (IgD multiple myeloma associated with light chain disease)--a case report.

INTRODUCTION Immunoglobulin D (IgD) myeloma is a rare disease, about 2% of all myelomas, even rarer when accompanied with another multiple myeloma in biclonal gammopathy. We presented a case of biclonal gammopathy-as-sociated manifestation of IgD myeloma and light chain disease in a patient who initially had renal failure. CASE REPORT 37-year-old male approximately one month before hospitalization began to feel malaise and fatigue along with decreased urination. Laboratory analysis revealed azotemia. A dialysis catheter was placed and hemodialysis started. The patient was then admitted to our hospital for further tests and during admission, objective examination revealed pronounced paleness with hepatosplenomegaly and hypertension (170/95 mmHg). Laboratory analysis showed erythrocyte sedimentation rate 122 mm/h, expressed anemic syndrome (Hb 71 g/L) and renal failure dialysis rank: creatinine 1,408 micromol/L, urea 31.7 mmol/L. There was two M components in serum protein electrophoresis: IgD lambda and free light chain lambda. Proteinuria was nephrotic rank (5.4 g/24 h), whose electrophoresis revealed 2 M components--massive in alpha 2 fraction of 71%; 7% in the discrete beta fraction, beta 2M / serum 110 mg / L, in urine 1.8 mg/L--extremely high; IgL kappa I lambda index 1:13 (reference value ratio 2:1). The findings pointed to double myeloma disease: IgD myeloma and Bence Jones lambda myeloma. Bone biopsy confirmed IgD myeloma lambda 100% infiltration medulla predominantly plasmablasts. The treatment continued with hemodialysis 3 times per week with chemotherapy protocol bortezomib, doxorubicin, dexamethasone. After 4 cycles of chemotherapy, there was a decrease of IgD, lamda-light chains, reduction in proteinuria (1.03 g/24 h), so hemodialysis was reduced to once per week. Six months after treatment initiation the patient underwent autologous bone marrow transplantation. In a 2-year follow-up period double myeloma disease showed complete remission. CONCLUSION The presented rare form of double myeloma disease with initial renal insufficiency underscores the importance of careful observation and teamwork that can alter the course of this serious disease.

Vascular access for hemodialysis via the iliac vessels.

Although creating vascular access for hemodialysis (HD) is a routine procedure in most cases, there are situations where routine approaches are no longer an option, and the surgeon needs to be creative in order to construct vascular access for rare and difficult cases (1-4). We present a 44-year-old man with dwarfism (28 kg, 100 cm), admitted to the hospital for creation of vascular access for HD. The patient was immobile because of multiple musculoskeletal deformities, but was fully alert and had preserved intelligence. The patient had developed kidney failure aged 22 because of multiple urinary tract anomalies. In the past the patient had Continuous Ambulatory Peritoneal Dialysis (CAPD) for two years, followed by HD three times a week for the last 20 years. Over the years, the patient also developed secondary chronic anemia, hyperparathyroidism and severe hypotension (BP=60/40 mmHg). After thrombosis of the last HD vascular access, right brachial artery was used for dialysis as a temporary solution with unsatisfactory results, and new vascular access was necessary. Color Doppler examination revealed that all major veins in the neck, arms, and legs were thrombosed. MSCT angiography of the lower limbs and pelvis, with phlebography of the pelvic veins revealed severe atherosclerotic changes on arterial vessels with preserved blood flow (Fig. 1). Because of patient posture and deformities, the abdominal wall was the only place accessible for a graft loop, and the right iliac vessels were the only option for vascular access (Fig. 1). The iliac vessels were accessed with an extra-peritoneal approach through a right Gibson incision. A polytetrafluoroethylene (PTFE) graft 5 mm, 50 cm long (GORE-TEX®, Stretch Vascular Graft, USA), was placed subcutaneously in a loop manner on the right side of the abdominal wall around the umbilicus. The graft was anastomosed to the external iliac artery and vein in “end-to-side” fashion, using PTFE CV-7 suture (GORE-TEX®, Sutures, USA) (Fig. 2). The patient was discharged home on the 10th postoperative day, and had his first successful HD using this graft twenty days later. The patient had anticoagulances following the operation (Fraxiparine 0,3 s.c.) for ten days. After that, the patient commenced maintenance therapy with warfarin. Similar angioaccess grafts have been used in the lower part of the abdominal wall (“bikini” bypass) as Hemla has suggested (5), but in this case femoral veins were thrombosed and we used iliac vessels. Moini et al. (6) reports the common iliac artery as an inflow in contrast to the external iliac artery which was more accessible in this case. Therefore, we decided to use an approach and vessels normally used during kidney transplant surgery. We used a 5 mm instead of a 6 mm graft which is usually advocated because of small caliber vessels with a greater chance of JV A _1 0_ 11 20 Fig. 1 MSCT angiography of the lower limbs and pelvis. Patient posture and multiple associated deformities can be seen in the picture depicted in the right corner.