A Prospective, Multinational Pharmacoepidemiological Study of Clinical Conversion to Sirolimus Immunosuppression after Renal Transplantation

This prospective pharmacoepidemiological study examined treatment and outcomes in patients converted to sirolimus (SRL) after renal transplantation. 484 subjects in 36 centres in 7 countries were followed for up to 5 years. Principal reasons for conversion were declining graft function (146/484, 30%) and side effects of prior therapy (144/484, 30%) and the major treatment combinations after conversion were SRL ± MMF (62%), SRL + TAC (21.5%), SRL + CSA (16.5%). The cumulative probability of biopsy-confirmed acute rejection (BCAR) was 5% (n=22), death-censored graft loss 12% (n=56) and death 6% (n=22), and there was no significant relationship to the treatment combination employed. Median calculated creatinine clearance was 48.4 (29.3, 64.5) mL/min at conversion, rising to 54.1 (41.2, 69.0) mL/min at month 1, 55.7 (39.0, 73.0) mL/min at month 12, 58.6 (39.7, 75.2) mL/min at two years and 60.9 (36.0, 77.0) mL/min at three years post-conversion. The most common adverse events were hypertension (47%), hyperlipidemia (26%), urinary tract infections (25%), anaemia (24%) and diarrhea (14%), and cardiac events, hyperlipemia and CMV infection were more common in patients converted during the first year. SRL was most frequently combined with MMF after conversion, but principal clinical outcomes were not significantly influenced by the treatment combination employed in normal practice.

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Graft function and pregnancy outcomes after kidney transplantation

BMC Nephrology ◽

10.1186/s12882-022-02665-2 ◽

2022 ◽

Vol 23 (1) ◽

Author(s):

Anke Schwarz ◽

Roland Schmitt ◽

Gunilla Einecke ◽

Frieder Keller ◽

Ulrike Bode ◽

...

Keyword(s):

Kidney Transplantation ◽

Renal Transplantation ◽

Pregnancy Outcomes ◽

Fetal Death ◽

Graft Loss ◽

Graft Function ◽

Trial Registration ◽

Control Group ◽

Kaplan Meier ◽

Egfr Decline

Abstract Background After kidney transplantation, pregnancy and graft function may have a reciprocal interaction. We evaluated the influence of graft function on the course of pregnancy and vice versa. Methods We performed a retrospective observational study of 92 pregnancies beyond the first trimester in 67 women after renal transplantation from 1972 to 2019. Pre-pregnancy eGFR was correlated with outcome parameters; graft function was evaluated by Kaplan Meier analysis. The course of graft function in 28 women who became pregnant after kidney transplantation with an eGFR of < 50 mL/min/1.73m2 was compared to a control group of 79 non-pregnant women after kidney transplantation during a comparable time period and with a matched basal graft function. Results Live births were 90.5% (fetal death n = 9). Maternal complications of pregnancy were preeclampsia 24% (graft loss 1, fetal death 3), graft rejection 5.4% (graft loss 1), hemolytic uremic syndrome 2% (graft loss 1, fetal death 1), maternal hemorrhage 2% (fetal death 1), urinary obstruction 10%, and cesarian section. (76%). Fetal complications were low gestational age (34.44 ± 5.02 weeks) and low birth weight (2322.26 ± 781.98 g). Mean pre-pregnancy eGFR was 59.39 ± 17.62 mL/min/1.73m2 (15% of cases < 40 mL/min/1.73m2). Pre-pregnancy eGFR correlated with gestation week at delivery (R = 0.393, p = 0.01) and with percent eGFR decline during pregnancy (R = 0.243, p = 0.04). Pregnancy-related eGFR decline was inversely correlated with the time from end of pregnancy to chronic graft failure or maternal death (R = -0.47, p = 0.001). Kaplan Meier curves comparing women with pre-pregnancy eGFR of ≥ 50 to < 50 mL/min showed a significantly longer post-pregnancy graft survival in the higher eGFR group (p = 0.04). Women after kidney transplantation who became pregnant with a low eGFR of > 25 to < 50 mL/min/1.73m2 had a marked decline of renal function compared to a matched non-pregnant control group (eGFR decline in percent of basal eGFR 19.34 ± 22.10%, n = 28, versus 2.61 ± 10.95%, n = 79, p < 0.0001). Conclusions After renal transplantation, pre-pregnancy graft function has a key role for pregnancy outcomes and graft function. In women with a low pre-pregnancy eGFR, pregnancy per se has a deleterious influence on graft function. Trial registration Since this was a retrospective observational case series and written consent of the patients was obtained for publication, according to our ethics’ board the analysis was exempt from IRB approval. Clinical Trial Registration was not done. The study protocol was approved by the Ethics Committee of Hannover Medical School, Chairman Prof. Dr. H. D. Troeger, Hannover, December 12, 2015 (IRB No. 2995–2015).

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The Role of Renal Transplantation in Systemic AL Amyloidosis.

Blood ◽

10.1182/blood.v106.11.3497.3497 ◽

2005 ◽

Vol 106 (11) ◽

pp. 3497-3497 ◽

Cited By ~ 1

Author(s):

Ashutosh D. Wechalekar ◽

Helen J. Lachmann ◽

Julian D. Gillmore ◽

Hugh J.B. Goodman ◽

Mark Offer ◽

...

Keyword(s):

Renal Failure ◽

Renal Transplantation ◽

Plasma Cell ◽

Graft Loss ◽

Graft Function ◽

Response To Treatment ◽

Plasma Cell Dyscrasia ◽

Al Amyloidosis ◽

Cytotoxic Treatment ◽

Significant Difference

Abstract Kidneys are the commonest site of amyloid deposition in AL amyloidosis (AL) and many patients present in advanced renal failure. Successful treatment of the underlying plasma cell dyscrasia may not prevent development of end stage renal failure and dialysis dependence. Even in the presence of good clonal response the prognosis of these patients on dialysis is poor with mortality being 3 times that for patients with diabetes (UK renal registry data 2003). Renal transplantation is controversial due to the systemic and progressive nature of AL amyloidosis. We report the experience with renal transplantation in 16 patients with AL seen at the National Amyloidosis Centre UK between 1986 and 2000. All patients had histologically proven amyloidosis with an underlying plasma cell dycrasia. None of the patients had extra-renal organ dysfunction. Median age at diagnosis of AL was 64 years (range 49–74) with 3 males and 13 females. 15 (93%) had monoclonal gammopathy as the underlying clonal disorder while 1 (7%) patient had Waldenstroms macroglobulinaemia. The median time from diagnosis of renal failure to renal transplantation was 5.5 yrs (range 0.3–17) including a median of 1.7 yrs on dialysis. Median age at renal transplantation was 56yrs (42–67). There were 2 (12%) live related renal transplants and 14 (88%) from cadaveric donors; there were no procedure-related deaths and none had primary graft non-function. Graft function remains well-preserved with the median creatinine clearance at last follow-up was 41.6 ml/min (range 25.1–68); the only cause of graft failure was death. 13 patients received cytotoxic treatment as follows: autologous stem cell transplantation (ASCT) 3 (18%), VAD chemotherapy 5 (31%), melphalan and prednisone 4 (25%), chlorambucil 1 (6%). 2 (15%) had a partial response to treatment while 11 (84%) had no response (this included the three patients with ASCT). The median age at death was 71.4 yrs. Six patients have died, all of progressive multi-organ amyloidosis, at a median 7.5yrs from renal transplantation (which is 12.2 yrs and 12.9 yrs respectively from the diagnosis of amyloidosis and ESRF). Four of these patients had evidence of amyloid accumulation in their renal graft. There was no significant difference in the median survival of patients with recurrent amyloid in the graft versus those without (p=0.78) and the only cause of graft loss was death with a functioning graft. The patients without amyloid in the graft had a trend for better OS (median not reached vs 12.9 yrs) and survival from renal transplantation (7.59 yrs vs. 5.5 yrs). In summary, this study shows that the overall survival of patients with predominant renal AL who underwent renal transplantation was remarkably good. Renal allograft survival was 7.4 yrs (median) despite a very poor haematological response to treatment in many patients. This study suggests that renal transplantation may have been underutilized in AL amyloidosis and should be considered in selected patients.

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Living unrelated (commercial) renal transplantation in children.

Journal of the American Society of Nephrology ◽

10.1681/asn.v961100 ◽

1998 ◽

Vol 9 (6) ◽

pp. 1100-1103

Author(s):

Y Frishberg ◽

S Feinstein ◽

A Drukker

Keyword(s):

Renal Transplantation ◽

Waiting Times ◽

Graft Function ◽

Best Interest ◽

Cadaveric Renal Transplantation ◽

Arab Children ◽

Calculated Creatinine Clearance ◽

Stage Renal Disease ◽

End Stage

Long waiting times for cadaveric renal transplantation has led the frustrated parents of Arab children with end-stage renal disease treated in our center to seek commercial renal transplantation (CRT) outside Israel. During the past 3 yr, 18 children, aged 13 +/- 1 yr, underwent CRT in one center in Iraq. Post-CRT follow-up was 20.2 +/- 2.5 mo. Immediate complications (abroad) included: death on the day of surgery (n = 1) and vascular thrombotic events requiring removal of a previously functioning graft (n = 2). There was a high incidence of urologic problems, mainly as a result of inadequate uretero-vesical anastomosis. Calculated creatinine clearance at 6, 12, 18, 24, and 30 mo was 84.7 +/- 6.4, 91.0 +/- 6.8, 90.8 +/- 6.2, 82.5 +/- 9.5, and 77.7 +/- 8.2 ml/min per 1.73 m2 respectively, representing excellent graft function in 13 patients and slightly compromised function in two children. One- and two-year patient survival was 94.4%, with a graft survival of 83.3%. CRT in these Arab children had a favorable outcome despite severe early postoperative complications. Graft function at follow-up was comparable to cadaveric renal transplantation in Israel. This may reflect a propensity for healthy young adult donors. Despite these results, the authors oppose and discourage the practice of CRT on legal and ethical grounds. Not to provide follow-up care in this specific group of patients would not have been in their best interest.

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Recurrent Glomerular Diseases in Renal Transplantation with Focus on Role of Electron Microscopy

Glomerular Diseases ◽

10.1159/000517259 ◽

2021 ◽

pp. 1-32

Author(s):

Surya V. Seshan ◽

Steven P. Salvatore

Keyword(s):

Electron Microscopy ◽

Renal Transplantation ◽

Kidney Disease ◽

Kidney Diseases ◽

Graft Loss ◽

Graft Function ◽

Vascular Lesions ◽

Glomerular Diseases ◽

Transplant Kidney ◽

Urine Testing

Background: The common causes of renal transplant complications include active or chronic rejection process, infections, and toxicity but also recurrent or de novo diseases, which play an important role in affecting long-term graft function or graft loss. Summary: Recurrent disease in renal transplantation is defined as recurrence of the original kidney disease leading to end-stage kidney disease. They comprise a heterogeneous group of predominantly glomerular and some tubulointerstitial and vascular lesions, which include primary kidney diseases (e.g., focal segmental glomerulosclerosis, membranous glomerulonephritis, and IgA nephropathy) or those secondary to systemic autoimmune, metabolic, and infectious processes that can range from subclinical to clinically overt acute, subacute, or chronic clinical presentations. In addition to the knowledge of prior renal disease and routine/periodic serum and urine testing for kidney function, a complete transplant renal biopsy examination is essential in the identification and differentiation of these diseases. The time of onset and severity of these diseases depend on the underlying etiopathogenetic mechanisms and the varied rates of recurrence in the early or late posttransplant period, often being modified by the current immunosuppressive protocols and other donor and recipient predisposing characteristics. Key Messages: Transplant kidney biopsy findings provide diagnostic accuracy and prognostic information regarding the potential for reversibility along with detection of unsuspected or clinically symptomatic recurrent diseases, with any concomitant rejection process or toxicity, for appropriate therapeutic decision-making. Routine electron microscopy in transplant kidney biopsies is a valuable tool in recognizing fully developed or early/subtle features of evolving recurrent diseases, often during the subclinical phases, in for cause or surveillance allograft biopsies.

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