Israel Medical Association Journal

Kidney involvement in systemic sclerosis (SSc) is common with altered kidney function present in approximately half of the patients [1]. Scleroderma renal crisis (SRC), the most severe kidney manifestation, occurs in about 20% of patients with this autoimmune disorder [1]. SRC mainly affects patients with the diffuse cutaneous systemic sclerosis (dcSSc) subtype of the disease, and particularly in those who are seropositive to anti RNA polymerase III antibodies [2]. In recent years, the prevalence of SRC has decreased following the initiation of medication therapy with angiotensin-converting-enzyme inhibitors (ACE-i). Previously, SRC mortality rates were as high as 78%. Contemporary studies in the post-ACE-i era suggest lower rates, with mortality rate ranging from 30% to 36% [3]. Nevertheless, progression to end-stage renal disease (ESRD) is evident and may require renal replacement therapies (RRTs). While renal transplant rates in SSc have increased, they constitute a small proportion of SSc-SRC patients (3–8%) and SSc-ESRD patients (4–17%).

Background: A limited program for kidney donation from uncontrolled donation after cardiocirculatory determination of death (uDCDD) was implemented at four hospitals in Israel in close cooperation with Magen David Adom (MDA), the national emergency medical service.

Objectives: To assess the outcome of transplantations performed between January 2017 and June 2022.

Methods: Donor data included age, sex, and cause of death. Recipient data included age, sex, and yearly serum creatinine levels. A retrospective study of out-of-hospital cardiac arrest cases treated by MDA during 2021 were analyzed to assess their compatibility as potential uDCDD donors.

Results: In total, 49 potential donors were referred to hospitals by MDA. Consent was obtained in 40 cases (83%), organ retrieval was performed in 28 cases, and 40 kidneys were transplanted from 21 donors (75% retrieval rate). At 1-year follow-up, 36 recipients had a functioning graft (4 returned to dialysis) and mean serum creatinine 1.59 ± 0.92 mg% (90% graft survival). Outcome after transplantation showed serum creatinine levels (mg%) at 2 years 1.41 ± 0.83, n=26; 3 years 1.48 ± 0.99, n=16; 4 years 1.07 ± 1.06, n=7; and 5 years 1.12 ± 0.31, n=5. One patient died of multiple myeloma at 3 years. The MDA audit revealed an unutilized pool of 125 potential cases, 90 of whom were transported to hospitals and 35 were declared dead at the scene.

Conclusions: Transplant outcomes were encouraging, suggesting that more intensive implementation of the program may increase the number of kidneys transplanted, thus shortening recipient waiting lists.

Candida species inhabit the gastrointestinal tract. Isolation of Candida from the respiratory tract has been found and reflects colonization, particularly among mechanically ventilated patients [1]. However, the existence of candida as a respiratory pathogen was previously doubted. Candida pneumonia is a rare and challenging-to-diagnose entity. We present a histopathologically confirmed case of necrotizing Candida pneumonia and lung abscess in a solid organ transplant recipient.

Background: Kidney transplantation is associated with early improvement in cardiac function and structure; however, data on cardiac adaptation and its relation to kidney allograft function remain sparse.

Objectives: To investigate the relationship between post-transplant kidney function and echocardiographic measures in patients with normal/preserved pre-transplant cardiac structure and function.

Methods: The study included 113 patients who underwent kidney transplantation at a single tertiary medical center from 2000 to 2012. The patients were evaluated by echocardiography before and after transplantation, and the relation between allograft function and echocardiographic changes was evaluated. Echocardiography was performed at a median of 510 days after transplantation.

Results: The post-transplantation estimated glomerular filtration rate (eGFR) was directly correlated with left ventricular (LV) systolic function and inversely correlated with LV dimensions, LV wall thickness, left atrial diameter, and estimated systolic pulmonary arterial pressure. In patients with significant allograft dysfunction (eGFR ≤ 45 ml/min), LV hypertrophy worsened, with no improvement in LV dimensions. In contrast, in patients with preserved kidney function, there was a significant reduction in both LV diameter and arterial pulmonary systolic pressure.

Conclusions: Our results show that in kidney transplant recipients, allograft function significantly affects cardiac structure and function. Periodic echocardiographic follow-up is advisable, especially in patients with kidney graft dysfunction.

Objectives: To test vitamin D levels in kidney transplant recipients residing closer to the equator, compare them to levels in liver transplant recipients and hemodialysis patients, and identify possible risk factors.

Methods: In a cross-sectional study 103 kidney transplant recipients, 27 liver transplant recipients and 50 hemodialysis patients followed at our institute were tested for vitamin D levels. Demographic data, medical history and current treatment were recorded from the medical files.

Results: Inadequate vitamin D levels (< 30 ng/ml) were found in 75% of all patients and 75% of all kidney transplant recipients. Vitamin D levels were higher among dialysis patients than transplant recipients, though deficiency rates were similar. No association was found between kidney function and vitamin deficiency. Deficiency was associated with higher prednisone doses, use of mycophenolate sodium, tacrolimus, and iron supplements, or lower doses of vitamin D supplementation.

Conclusions: Despite potential higher ultraviolet B exposure, inadequate vitamin D levels were prevalent in our study group. Importantly, some immunosuppressive medications were associated with vitamin D deficiency and high doses of vitamin D were associated with less deficiency.

Background: Amyloidosis of familial Mediterranean fever (FMF) may lead to end-stage renal failure, culminating in kidney transplantation. Since amyloidosis is prompted by high serum amyloid A (SAA) levels, increased SAA is expected to persist after transplantation. However, no data are available to confirm such an assumption.

 Objectives: To determine SAA levels in kidney-transplanted FMF-amyloidosis patients and evaluate risk factors for the expected high SAA levels in this patient group.

Methods: SAA, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) values were obtained from 16 kidney-transplanted FMF-amyloidosis patients, 18 FMF patients without amyloidosis and 20 kidney-transplanted patients with non-inflammatory underlying disease. Demographic, clinical and genetic risk factors evaluation was based on data extracted from files, interviews and examination of the patients.

Results: SAA level in FMF patients who underwent kidney transplantation due to amyloidosis was elevated with a mean of 21.1 ± 11.8 mg/L (normal ≤ 10 mg/L). It was comparable to that of transplanted patients with non-inflammatory disorders, but tended to be higher than in FMF patients without amyloidosis (7.38 ± 6.36, P = 0.08). Possible risk factors for the elevated SAA levels in kidney transplant patients that were excluded were ethnic origin, MEFV mutations, gender, age and disease duration.

Conclusions: Kidney-transplanted patients with FMF-amyloidosis and with other non-FMF causes displayed mildly elevated SAA levels, possibly resulting from exposure to foreign tissue rather than from various FMF-related factors. 

Background: Recent advances in immunosuppressive therapy have led to a substantial improvement in the outcome of kidney transplantation. Living unrelated donors may become a source of additional organs for patients on the kidney waiting list.

Objectives: To study the impact of combination of calcineurin inhibitors and mycophenolate-mofetile, together with steroids, on outcomes of living related and unrelated transplants. 

Methods: Between September 1997 and January 2000, 129 patients underwent living related (n=80) or unrelated (n=49) kidney transplant. The mean follow-up was 28.2 months. Immunosuppressive protocols consisted of MMF[1] with cyclosporine (41%) or tacrolimus (59%), plus steroids. Patient and graft survival data, rejection rate, and graft functional parameters were compared between the groups.

Results: LUD[2] recipients were older (47.8 vs. 33.6 years) with higher number of re-transplants (24.5% vs. 11.2% in LRD[3] recipients, P < 0.05). Human leukocyte antigen matching was higher in LRD recipients (P < 0.001). Acute rejection developed in 28.6% of LUD and 27.5% of LRD transplants (P = NS). Creatinine levels at 1, 2 and 3 years post-transplant were 1.6, 1.7 and 1.7 mg/dl for LRD patients and 1.5, 1.5 and 1.3 mg/dl for LUD recipients (P = NS). There was no difference in patient survival rates between the groups. One, 2 and 3 year graft survival rates were similar in LRD (91.3%, 90% and 87.5%) and LUD (89.8%, 87.8% and 87.8%) recipients.

Conclusions: Despite HLA[4] disparity, rejection and survival rates of living unrelated transplants under current immunosuppressive protocols are comparable to those of living related transplants.

Background: Leptin is a 16 kDa hormone synthesized by adipocytes and involved in body weight regulation.

Objectives: To determine serum leptin concentrations in heart, liver and kidney transplant recipients.

Methods: We investigated 57 patients: 18 male heart transplant recipients (age 25-69 years) at 1-66 months after transplantation, 6 female and 8 male liver transplant recipients (age 33-70) at 11-73 months after transplantation, and 10 female and 15 male kidney transplant recipients (age 20-61) at 3-138 months after transplantation. All recipients were receiving immunosuppressive therapy, including prednisone 0-20 mg/day, azathioprine 75-125 mg/day, cyclosporin 100-250 mg/day or tacrolimus 2-10 mg/day. The results were compared to those of 10 female and 10 male healthy controls. Morning serum concentrations of leptin were measured with a commercial radioimmunoassay (Linco Research Inc., USA), and serum insulin and cortisol levels were measured by radioimmunoassay.

Results: Patients (both men and women) after heart, liver and kidney transplantation exhibited significantly higher serum concentrations of leptin and leptin/body mass index ratios than controls. Serum leptin concentrations were significantly higher in women than in men and correlated very significantly with BMI[1] in all cases. The multivariate stepwise analyses showed that among parameters including BMI, gender, age, time after transplantation, prednisone dose, hematocrit, serum concentrations of glucose, albumin, creatinine, cortisol and insulin, only BMI, gender, cortisol and insulin were significant independent determinants of serum leptin levels in these patients.

Conclusions: This is the first report showing that, in addition to body mass index and gender, basal cortisol and insulin levels affect the hyperleptinemia in transplant patients. The clinical relevance of hyperleptinemia in these patients will require further investigation.

Background: In simultaneous pancreas-kidney transplantation, with both organs coming from the same donor, the addition of a pancreas to the kidney transplant does not jeopardize the kidney allograft outcome despite higher postoperative SPK morbidity. Pancreas allograft outcome has recently improved due to better organ selection and more accurate surgical techniques.

Objective: To demonstrate the positive impact of SPK on kidney allograft outcome versus kidney transplantation alone in insulin-dependent diabetes mellitus patients with end-stage renal failure.

Methods: We performed 39 consecutive SPKs in 14 female and 25 male IDDM patients with renal failure after an average waiting time of 9 months. Multi-organ donor age was 30 years (range 12-53). The kidneys were transplanted in the left retroperitoneal iliac fossa following completion of the pancreas transplantation; kidney cold ischemia time was 16±4 hours. Induction anti-rejection therapy was achieved with polyclonal antithymocytic globulin and methylprednisolone, and maintenance immunosuppression by triple drug therapy (prednisone, cyclosporine or tacrolimus, and azathioprine or mycophenolate mofetil). Infection and rejection were closely monitored.

Results: All kidney allografts produced immediate urinary output following SPK. Two renal grafts had mild function impairment due to acute tubular damage but recovered after a short delay. Three patients died from myocardial infarction, cerebrovascular event and abdominal sepsis on days 1, 32 and 45 respectively (1 year patient survival 92%). An additional kidney allograft was lost due to a renal artery pseudo-aneurysm requiring nephrectomy on day 26. Nineteen patients (49%) had an early rejection of the kidney that was resistant to pulse-steroid therapy in 6. No kidney graft was lost due to rejection. Patients with acute kidney-pancreas rejection episodes suffered from severe infection, which was the main cause of morbidity with a 55% re-admission rate. Complications of the pancreas allograft included graft pancreatitis and sepsis, leading to a poor kidney outcome with sub-optimal kidney function at 1 year. Kidney graft survival at one year was 89% or 95% after censoring the data for patients who died with functioning grafts.

Conclusions: Eligible IDDM patients with advanced diabetic nephropathy should choose SPK over kidney transplantation alone from either a cadaver or a living source.

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SPK= simutaneous pancreas-kidney transplatation

IDDM= insulin-dependent diabetes mellitus