Second and Third Chance to Stop Having Diabetes. Pancreas Retransplant With Functional Kidney Graft: A Single-Center Experience.

BACKGROUND: Simultaneous pancreas-kidney (SPK) transplant is the primary option in patients with type 1 diabetes mellitus who develop end-stage kidney disease. Pancreas retransplant (PRt) has become an alternative in patients who experience pancreas graft failure (PGF). There is a lack of evidence regarding PRt in international registers. There are small series of published research with indeed heterogeneous results. We aim to compare PRt outcomes with primary SPK transplant in our center. METHODS: The study was designed as a descriptive study of a cohort of 234 patients who received SPK transplant and received another PRt because of PGF at Reina Sofía University Hospital between 1988 and 2021. Kaplan-Meier analysis was performed to calculate patient and allograft survival. RESULTS: Of these 234 SPK transplants, 53 pancreas grafts (22.6%) were lost initially. In total, 15 PRts were performed. The major cause of first PGF was surgical, whereas the medical cause was the most frequent in the PRt group. There were 60 deaths in the SPK group compared with only 1 in the PRt group. In Kaplan-Meier analysis, the PRt group showed worse survival than the SPK group, with statistically significant difference between groups (P = .05). Patient survival was not different between both groups. CONCLUSIONS: PRt constitutes a viable option for recipients who experience PGF in the absence of formal contraindication. Although graft retransplant survival seems to be inferior to first graft in our series, these results are difficult to compare because of the scarce number of procedures performed.

Long-term Kidney Function Evolution in Living Kidney Donors: A Single Center Experience.

Living donor kidney transplant is the best treatment for end-stage kidney disease, posing minimal perioperative morbimortality for the donor, although long-term consequences are subject of debate if donor acceptance widens. We present a retrospective observational study analyzing clinical, demographic, and analytical variables throughout the follow-up period of 60 kidney donors whose procedures were performed between 1985 and 2021 at our hospital. Donors were divided according to their previous high blood pressure status, analyzing kidney function and other clinical parameters throughout follow-up. There were no statistically significant differences, although there was a trend toward a higher uric acid levels and lower high-density lipoprotein cholesterol in predonation patients with hypertension, not yielding an excess of end-stage kidney disease between groups at the end of the follow-up. We also analyzed the evolution of estimated glomerular filtration rate (eGFR), dividing patients into tertiles, which resulted in none of the parameters associating a higher rate of progression. All donors had an eGFR >71 mL/min/1.73 m2 at the time of donation. Over time, a decline in eGFR <60 mL/min/m/1.73 m2 was observed in 26 patients (53.6%), measured by Chronic Kidney Disease Epidemiology Collaboration estimation and in 55.4% of the total (31 patients) by Modification of Diet in Renal Disease. At our center, kidney donors with adequate predonation eGFR, although presenting a reduction in postnephrectomy eGFR, remain stable afterward, with none of them reaching an eGFR <30 mL/min/1.73 m2. We found no differences in the impact of high blood pressure on long-term eGFR, nor predictive factors influencing the rate of eGFR decline. Studies with larger number of patients are needed to confirm these results.

First Report in the Literature of Biopsy-Proven Noncollapsing Focal Segmental Glomerulosclerosis Relapse in a Second Renal Transplant Presenting With Thrombotic Microangiopathy: A Case Report.

Primary focal segmental glomerulosclerosis (FSGS) is a podocytopathy with an irregular response to immunosuppressive therapies. FSGS relapse occurs in 30% to 80% of kidney grafts, and poor survival outcomes include large proteinuria and the nephrotic syndrome's cardinal clinical features. Thrombotic microangiopathy (TMA) is caused by endothelial injury due to complement dysregulation including acute kidney injury, proteinuria, and severe hypertension common renal presentations. Both pathologies have well-described genetic forms, but their relationship remains uncertain. FSGS lesions can be found in kidney biopsy specimens in patients with TMA, and TMA has been reported in patients with collapsing glomerulopathy. However, this combination has not been clearly described in renal transplant recipients. We present the case of a 22-year-old man who received his second kidney allograft and developed an early graft disfunction with nephrotic syndrome and clinical TMA. His background was remarkable for primary, biopsy-confirmed FSGS in childhood, and he started hemodialysis in 2006 and received a living donor kidney graft the same year. He presented with a FSGS relapse with malignant hypertension and seizures in the first posttransplant month and had an irregular response to plasma exchange and rituximab, and dialysis was reinitiated 10 years later. A total of 3 biopsies were performed after his second kidney transplant showing the evolution of a FSGS relapse with histologic and clinical TMA in the absence of identified genetic mutations. Partial responses to treatments with plasma exchange, eculizumab, and rituximab were obtained, but the allograft was lost after 26 months. This case is the first report of concomitant FSGS and TMA in a renal transplant recipient.

Case Report: Successful Response to Intravenous Immunoglobulin and Steroid Pulses in a Renal Transplant Recipient With Severe Covid-19 Disease and Associated Acute Allograft Failure.

The impact of Covid-19 pneumonia caused by SARS-CoV-2 on transplanted populations under chronic immunosuppression seems to be greater than in normal population. Clinical management of the disease, particularly in those patients worsening after a cytokine storm, with or without allograft impairment and using available therapeutic approaches in the absence of specific drugs to fight against the virus, involves a major challenge for physicians. We herein provide evidence of the usefulness of high-dose intravenous immunoglobulin (IVIG) combined with steroid pulses to successfully treat a case of Covid-19 pneumonia in a single-kidney transplanted patient with mechanical ventilation and hemodialysis requirements in the setting of a cytokine storm. A rapid decrease in the serum level of inflammatory cytokines, particularly IL-6, IL-8, TNF-α, MCP-1 and IL-10, as well as of acute-phase reactants such as ferritin, D-dimer and C-reactive protein was observed after the IVIG infusion and methylprednisolone bolus administration with a parallel clinical improvement and progressive allograft function recovery, allowing the patient's final discharge 40 days after the treatment onset. The immunomodulatory effect of IVIG together with the anti-inflammatory and immunosuppressive potential of steroids could be an alternative strategy to treat severe cases of Covid-19 pneumonia associated with an uncontrolled inflammatory response in transplanted populations.

Haemodialysis using high cut-off dialysers for treating acute renal failure in multiple myeloma.

INTRODUCTION: Acute renal failure (ARF) occurs in 12%-20% of all multiple myeloma (MM) cases, and the survival of these patients depends on renal function recovery. Renal function is not recovered in 75% of dialysis-dependent patients, and their mean survival with replacement therapy is less than one year. Renal tubular disease is the most frequent cause of renal failure. It is present in more than 55% of renal failure cases and in 75% of those requiring dialysis. Rapid reduction of free light chain levels in the blood is necessary in order to recover renal function. One coadjuvant measure in treating the disease is reducing light chain levels with plasmapheresis, but its efficacy has not yet been clearly proven. Our proposal was therefore to use extended haemodialysis sessions with high cut-off dialysers (HCO-HD), obtaining a recovery rate of more than 60%. We present the progress of 6 patients with myeloma and acute renal failure who were treated with HCO-HD and the complications associated with using this type of haemodialysis. Then, we review the pros and cons of this technique. METHOD: Six patients diagnosed with MM and ARF requiring dialysis and with serum free light chain levels above 500 mg/l were treated with 8-hour haemodialysis sessions with an HCO-HD filter. Before and after each session, serum free light chain levels were measured by nephelometry; other parameters were recorded as well. At the same time, patients underwent chemotherapy according to protocols. RESULTS: The symptom onset times of the 3 men and 3 women diagnosed with MM and ARF were highly variable, from 7 days to more than 1 year. We performed 90 extended sessions with HCO-HD filters, and each patient underwent between 6 and 40 sessions. Free light chain levels decreased by a mean of 65% between treatment onset and completion, except in one patient who experienced a 12.6% reduction. The mean percentage of reduction of light chain levels per session was 54.98% ± 17.27%. A complication occurred during 28% of the sessions. Of these complications, 48% were due to system coagulation. There were no major changes in pre-dialysis albumin, calcium, phosphorous or magnesium levels, although lower values that were not clinically relevant were recorded in one case. Renal function was recovered in 3 patients, they are alive and dialysis-free. In biopsied cases that recovered renal function, the specimen showed tubular nephropathy only. Those patients who took longer to be diagnosed did not recover their renal function, and when biopsied, they were diagnosed with renal tubular disease and light chain deposition disease. CONCLUSION: We found extended haemodialysis with HCO-HD filters to be a reasonable alternative in ARF caused by renal tubular disease, and achieved a recovery rate of 50% in our cases. Function recovery was influenced by the elapsed time between symptom onset and myeloma diagnosis, histological findings, promptness of starting chemotherapy, response to chemotherapy, and effectiveness of light chain extraction. In any case, further studies are needed to examine new chemotherapy agents and new direct free light chain removal techniques.

Tratamiento con hemodiálisis del fracaso renal agudo en el mieloma múltiple con filtros de alto poro (high cut-off) / Haemodialysis using high cut-off dialysers for treating acute renal failure in multiple myeloma

Introducción: El fracaso renal agudo (FRA) en el mieloma múltiple (MM) se presenta entre el 12-20% de los casos y la supervivencia de estos pacientes depende de la recuperación de la función renal. El 75% de los pacientes dependientes de diálisis no recuperan la función renal y su supervivencia media en situación de tratamiento sustitutivo es inferior al año. La nefropatía por cilindros es la causa más frecuente de fracaso renal y acontece en más del 55% de los casos, y en el 75% de aquellos que requieren diálisis. Para facilitar la recuperación de la función renal es imprescindible la disminución rápida de los niveles en sangre de cadenas ligeras. Una medida coadyuvante al tratamiento específico de la enfermedad ha sido la reducción de estas cadenas ligeras con plasmaféresis, sin que se haya demostrado claramente su eficacia, por lo que se ha propuesto el uso de hemodiálisis largas con filtros de alto poro (HCO), consiguiendo una tasa de recuperación superior al 60%. Presentamos la evolución en seis casos de pacientes con mieloma y fracaso renal agudo que fueron tratados con dichos filtros HCO, las complicaciones con este tipo de hemodiálisis y revisamos los pros y los contras de esta técnica. Metodología: Seis pacientes diagnosticados de MM y FRA con necesidad de diálisis y niveles circulantes de cadena ligera por encima de 500 mg/l fueron tratados con hemodiálisis de 8 horas con filtro HCO. Al comienzo y al final de cada sesión se medían las cadenas ligeras séricas por nefelometría, así como otros parámetros. Al mismo tiempo los pacientes fueron tratados con quimioterapia según protocolos. Resultados: A tres hombres y tres mujeres diagnosticados de MM y FRA, con inicio de los síntomas muy variable, desde 7 días a más de un año, se les realizó 90 sesiones de hemodiálisis largas con filtros HCO con un rango de entre 6 y 40 sesiones. El porcentaje de reducción de las cadenas ligeras desde el inicio del tratamiento hasta su finalización fue el 65% de media, excepto en un paciente, que fue del 12,6%. La media del porcentaje de reducción de la cadena ligera por sesión fue de 54,98 ± 17,27%. En el 28% de las sesiones se registró alguna complicación. El 48% de las complicaciones se debieron a la coagulación del sistema. No hubo grandes cambios en los niveles de albúmina prediálisis, calcio, fósforo y magnesio, aunque en algún caso se registraron valores disminuidos que no comportaron relevancia clínica. En tres pacientes la función renal se recuperó y permanecen vivos e independientes de la diálisis. En los casos biopsiados y que recuperaron función renal, la nefropatía por cilindros fue pura. Los pacientes que tardaron más en ser diagnosticados fueron los pacientes que no recuperaron función renal, y cuando se les efectuó biopsia el diagnóstico fue de nefropatía por cilindros más enfermedad por depósitos. Conclusión: En nuestra experiencia, la hemodiálisis larga con filtros HCO es una alternativa razonable en el FRA causado por nefropatía por cilindros, alcanzando en nuestros casos una tasa de recuperación del 50%. En la recuperación influyeron: el tiempo transcurrido desde el inicio de los síntomas al diagnóstico de mieloma, los hallazgos histológicos, la rapidez de instauración del tratamiento quimioterápico y su respuesta y la eficacia en la extracción de cadenas ligeras. En cualquier caso, son necesarios nuevos estudios con nuevos agentes quimioterápicos y las nuevas técnicas de extracción directa de cadenas ligeras (AU)

Introduction: Acute renal failure (ARF) occurs in 12%-20% of all multiple myeloma (MM) cases, and the survival of these patients depends on renal function recovery. Renal function is not recovered in 75% of dialysis-dependent patients, and their mean survival with replacement therapy is less than one year. Renal tubular disease is the most frequent cause of renal failure. It is present in more than 55% of renal failure cases and in 75% of those requiring dialysis. Rapid reduction of free light chain levels in the blood is necessary in order to recover renal function. One coadjuvant measure in treating the disease is reducing light chain levels with plasmapheresis, but its efficacy has not yet been clearly proven. Our proposal was therefore to use extended haemodialysis sessions with high cut-off dialysers (HCO-HD), obtaining a recovery rate of more than 60%. We present the progress of 6 patients with myeloma and acute renal failure who were treated with HCO-HD and the complications associated with using this type of haemodialysis. Then, we review the pros and cons of this technique. Method: Six patients diagnosed with MM and ARF requiring dialysis and with serum free light chain levels above 500mg/l were treated with 8-hour haemodialysis sessions with an HCO-HD filter. Before and after each session, serum free light chain levels were measured by nephelometry; other parameters were recorded as well. At the same time, patients underwent chemotherapy according to protocols. Results: The symptom onset times of the 3 men and 3 women diagnosed with MM and ARF were highly variable, from 7 days to more than 1 year. We performed 90 extended sessions with HCO-HD filters, and each patient underwent between 6 and 40 sessions. Free light chain levels decreased by a mean of 65% between treatment onset and completion, except in one patient who experienced a 12.6% reduction. The mean percentage of reduction of light chain levels per session was 54.98%±17.27%. A complication occurred during 28% of the sessions. Of these complications, 48% were due to system coagulation. There were no major changes in pre-dialysis albumin, calcium, phosphorous or magnesium levels, although lower values that were not clinically relevant were recorded in one case. Renal function was recovered in 3 patients, they are alive and dialysis-free. In biopsied cases that recovered renal function, the specimen showed tubular nephropathy only. Those patients who took longer to be diagnosed did not recover their renal function, and when biopsied, they were diagnosed with renal tubular disease and light chain deposition disease. Conclusion: We found extended haemodialysis with HCO-HD filters to be a reasonable alternative in ARF caused by renal tubular disease, and achieved a recovery rate of 50% in our cases. Function recovery was influenced by the elapsed time between symptom onset and myeloma diagnosis, histological findings, promptness of starting chemotherapy, response to chemotherapy, and effectiveness of light chain extraction. In any case, further studies are needed to examine new chemotherapy agents and new direct free light chain removal techniques (AU)