Ernst-Heinrich Scheuermann

Long‐Term Consequences of Live Kidney Donation Follow‐Up in 93% of Living Kidney Donors in a Single Transplant Center

Live kidney donation is increasing rapidly. Increases of blood pressure and proteinuria but no accelerated loss of renal function in kidney donors have been described. The credibility of this research is hampered by retrieval rates of only 50–70% of donors.

Switch to a Sirolimus‐Based Immunosuppression in Long‐Term Renal Transplant Recipients: Reduced Rate of (Pre‐)Malignancies and Nonmelanoma Skin Cancer in a Prospective, Randomized, Assessor‐Blinded, Controlled Clinical Trial

Renal transplant recipients (RTR) have a 50–200‐fold higher risk for nonmelanoma‐skin cancer (NMSC) causing high rates of morbidity and sometimes mortality. Cohort‐studies gave evidence that a sirolimus‐based immunosuppression may inhibit skin tumor growth. This single‐center, prospective, assessor‐blinded, randomized trial investigated if switching to sirolimus treatment inhibits the progression of premalignancies and moreover how many new NMSC occur compared to continuation of the original immunosuppressive therapy. Forty‐four RTR (mean age 59.9 years, mean duration of immunosuppression 229.5 months) with skin lesions were randomized to sirolimus or continuation of their original immunosuppression. Blinded dermatological assessment at month 6 and 12 by the same dermatologist evaluated the clinical change compared to baseline. Biopsy was performed in suspected malignancy. Already the 6‐month‐assessment showed significant superiority of sirolimus‐therapy: a stop of progression, even regression of preexisting premalignancies (p < 0.0005). This effect was increased at month 12 (p < 0.0001). Nine patients developed histologically confirmed NMSC: one in the sirolimus group, eight in the control group, p = 0.0176. Sirolimus‐based immunosuppression in RTR, even when established many years after transplantation, can delay the development of premalignancies, induce regression of preexisting lesions and decelerate the incidence of new NMSC.

Abrogation of nephrotic proteinuria by rituximab treatment in a renal transplant patient with relapsed focal segmental glomerulosclerosis

Relapse of focal segmental glomerulosclerosis (FSGS) after renal transplantation is 20–40%. Recurrence after a first relapse is 80%. The only current treatment is plasmapheresis and/or cyclophosphamide. We report successful treatment of a second relapse in a 48‐year‐old patient. At age 33, FSGS was diagnosed. The patient began hemodialysis 1 year later. In her first renal transplant, she developed recurrent FSGS and reached terminal transplant failure 3 years later. Eight years later, a second transplant was performed. Immunosuppressive regimen: steroids, mycophenolate mofetil (MMF), tacrolimus (TAC), and rabbit anti‐thymocyte globulin. Proteinuria of 2–6 g/day was detected and a biopsy showed recurrent FSGS. Plasmapheresis was started without success. Another biopsy still showed FSGS. The patient received two doses of rituximab (375 mg/m2 each) i.v. Three weeks later, proteinuria was 350 mg/day (serum‐creatinine 1.6 mg/dl). Twelve months later, proteinuria was at 90 mg/day. Rituximab might be an option for recurrent FSGS after renal transplantation.

Anti-inflammatory effects of clopidogrel intake in renal transplant patients: Effects on platelet-leukocyte interactions, platelet CD40 ligand expression, and proinflammatory biomarkers

Increased platelet activation has been described during treatment with various immunosuppressive agents and may contribute to the high cardiovascular mortality rate in renal transplant patients. Platelets are thought to propagate the inflammatory process of atherosclerosis by interaction with leukocytes.

Pathophysiology of Cyclosporine-Induced Nephrotoxicity in Humans: A Role for Nitric Oxide?

Background: The causes for the nephrotoxicity of cyclosporine A (CsA) have not been fully elucidated. Intrarenal vasoconstriction induced by several different mediators, both in humans and experimental animals, have been proposed. Methods: We studied prostaglandin metabolites, endothelin and nitric oxide in kidney transplant patients receiving their first CsA dose. Prostaglandin metabolites in the urine and endothelin and nitric oxide (NO2/NO3) in urine and plasma were measured in 14 patients before and 3 and 6 h after oral ingestion of CsA (10 mg/kg b.w.). Clearances for inulin and p-aminohippuric acid (PAH) were measured before and in two separate 3-hour periods after CsA. Blood pressure, heart rate, and CsA blood levels were also determined. Results: Clearances of inulin and PAH decreased progressively after CsA dosage while renal vascular resistance increased. Nitric oxide plasma levels decreased in nearly all patients from 21.0 ± 2.8 to 19.1 ± 2.6 (p = 0.003) and then rose slightly to 19.5 ± 2.5 µmol/l (p = 0.1) 3 and 6 h after CsA ingestion, respectively. Urinary excretion of NO2/NO3 decreased nonsignificantly from 269 ± 38.8 to 259 ± 27.7 and 254 ± 41.6 µmol/min (p = 0.5 and 0.5). At the same time, urinary prostaglandin E2 and 6-keto-prostaglandin F1α excretion rate declined significantly [from 1,187 ± 254 to 1,186 ± 351 and 730 ± 148 pg/min (p = 0.27 and 0.02) and from 697 ± 115 to 645 ± 134 and 508 ± 58.2 pg/min (p = 0.34 and 0.05)]. Urinary thromboxane B2 and plasma and urinary endothelin first increased and then decreased nonsignificantly. Mean arterial pressure rose from 107 ± 2.5 to 110 ± 2.6 and 114 ± 3.4 mm Hg (p = 0.1 and 0.05). Conclusion: The pathophysiology of CsA-induced acute renal vasoconstriction involves several different mechanisms including a decrease of the vasodilating prostaglandins E2 and 6-keto-prostaglandin F1α and possibly nitric oxide.

De novo renal cell carcinoma of native and graft kidneys in renal transplant recipients

Study Type – Therapy (case series)

Development of urological cancers in renal transplant recipients: 30‐year experience at the Frankfurt Transplant Center

Fatal post‐transplant malignancies with a high proportion of genitourinary neoplasms represent a serious long‐term challenge. With continuous improvement of the allograft and patient survival, cancer development after renal transplantation may soon turn to the leading morbidity cause. In a retrospective single‐center study of 1990 renal transplant recipients between November 1979 and November 2009, records of patients with urological neoplasms including epidemiological, clinical and survival parameters were accessed. Sixty‐six de novo urological malignancies in 58 recipients were recorded in the study period, being most common after skin cancers (15.6% of enregistered tumors). From these, 29 were renal cell cancers, including five neoplasms of transplanted kidney, 24 transitional cell carcinomas, 11 prostate carcinomas, and two germ cell carcinomas with incidence rates of 1.5%, 1.2%, 0.9% and 0.2%, respectively. The patient follow up was virtually complete. Tumor‐related death was found in 44% of cases. By multivariate analysis, no influence of either duration of dialysis, mode or duration of immunosuppression, gender or age at transplantation on overall patient survival could be demonstrated. This study, documenting a 30‐year single center experience, emphasizes the increased risk for urological neoplasms occuring after renal transplantation. Screening strategies for urological cancers should be optimized. (Cancer Sci 2010; 101: 2430–2435)

Immunosuppressive therapy regimen and platelet activation in renal transplant patients

Increased platelet activation caused by an immunosuppressive therapy regimen may contribute to the high incidence of death from cardiovascular disease in renal transplant patients. Cyclosporine (INN, ciclosporin) and azathioprine are reported to activate platelets, but data are rare and controversial for tacrolimus and mycophenolate mofetil.

Reactivation of hepatitis B two years after rituximab therapy in a renal transplant patient with recurrent focal segmental glomerulosclerosis: a note of caution.

Abstract:  We report on the reactivation of hepatitis B in a renal transplant patient who had been treated with rituximab for recurrent focal segmental glomerulosclerosis two and a half yr previously. He lost his anti‐hepatitis B surface antigens and anti‐hepatitis B core antigen antibodies and developed hepatitis B virus (HBV)‐DNA positive hepatitis. Hepatitis C, which had been successfully treated by alpha interferon 10 yr before, remained quiescent. We suggest regular controls of HBV‐DNA, anti‐HBV antibodies and transaminases for prolonged periods in patients with status post‐hepatitis B treated with rituximab. Prophylactic therapy with lamivudine and/or hepatitis B hyperimmune globulin may be considered in patients with a decrease in anti‐HBV antibodies.

Multiple adenomas and hepatocellular carcinoma in a renal transplant patient with glycogen storage disease type 1a (von Gierke disease).

We report on a 42-year-old female patient with glycogen storage disease type 1a (von Gierke disease, GSD 1a) who developed hepatic adenomas and finally a hepatocellular carcinoma 10 years after renal transplantation. The tumor was resected; however, the patient died 6 months later as a result of fulminant carcinoma recurrence. In patients who have GSD 1a with terminal renal failure, combined liver and kidney transplantation may be considered at an early stage of the disease.