Kidney transplantation in patients with multiple myeloma: narrative analysis and review of the last 2 decades

2020 ◽  
Author(s):  
David W Chitty ◽  
Monique A Hartley-Brown ◽  
Mersema Abate ◽  
Richa Thakur ◽  
Rimda Wanchoo ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Kidney Transplantation ◽  
Kidney Disease ◽  
Kidney Transplant ◽  
Narrative Analysis ◽  
Case Series ◽  
Kidney Transplant Recipients ◽  
Course Of Illness ◽  
Kidney Impairment

Abstract There have been significant advances in the treatment of multiple myeloma in the last 2 decades. Approximately 25% of patients with newly diagnosed myeloma have some degree of kidney impairment. During the course of illness, nearly 50% of myeloma patients will develop kidney disease. Moreover, approximately 10% of myeloma patients have advanced kidney disease requiring dialysis at presentation. Hemodialysis is associated with a significantly reduced overall survival. In the setting of prolonged long-term overall survival due to the use of newer immunotherapeutic agents in the treatment of myeloma, patients with myeloma and advanced kidney disease may benefit from more aggressive management with kidney transplantation. Unfortunately, most data regarding outcomes of kidney transplantation in patients with myeloma come from single center case series. With the advent of novel treatment choices, it remains unclear if outcomes of kidney transplant recipients with myeloma have improved in recent years. In this descriptive systematic review, we coalesced published patient data over the last 20 years to help inform clinicians and patients on expected hematologic and kidney transplant outcomes in this complex population. We further discuss the future of kidney transplantation in patients with paraproteinemia.

Kidney transplant in multiple myeloma, the challenges, and potentials

2020 ◽  
Vol 4 (1-2) ◽  
pp. 15-17
Author(s):  
Nelson Leung
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Kidney Transplantation ◽  
Kidney Transplant ◽  
Kidney Failure ◽  
Residual Disease ◽  
Graft Loss ◽  
Disease Assessment ◽  
Improve Patient Selection ◽  
Pros And Cons

Kidney failure is a common sequela of multiple myeloma. Tremendous progress in this disease over the past two decades has resulted in more than doubling of the median survival. Despite that, patients with irreversible kidney failure still have inferior outcomes as compared to those with intact kidney function. Kidney transplantation in these patients remains controversial. In this issue of Journal of Onco-Nephrology, two groups of clinicians caring for these patients debate the pros and cons of kidney transplantation in this population. The improvement of overall survival to 7.7 years in patients under the age of 65 years is a strong arg for kidney transplantation. In addition, the use of fluorescent in situ hybridization in risk assessment and minimal residual disease assessment for hematologic response could substantially improve patient selection for kidney transplantation. On the other hand, myeloma remains incurable and kidney failure itself is a high-risk feature. Despite advances, kidney transplantation in myeloma patients continues to present challenges with multiple myeloma relapse, rejection, and infection resulting in higher number of graft loss and death. Whether kidney transplant should be performed in patients with multiple myeloma currently remains debatable, but it may not be long before overall survival and disease control improve to the point where withholding kidney transplantation would be unethical. The questions in preparation for that day are should myeloma patients be held to the same metrics as patients without myeloma and if no, then what would be an acceptable overall and graft survival? Once the answers have been agreed upon by the experts and the governing bodies for transplantation, then proper clinical trials can be designed so that benefits can be optimized and precious resources not be wasted.

scholarly journals Plasma Nitration of High-Density and Low-Density Lipoproteins in Chronic Kidney Disease Patients Receiving Kidney Transplants

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Ahmed Bakillah ◽  
Fasika Tedla ◽  
Isabelle Ayoub ◽  
Devon John ◽  
Allen J. Norin ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Transplantation ◽  
Kidney Disease ◽  
Kidney Transplant ◽  
Sandwich Elisa ◽  
High Density ◽  
Hiv Protease ◽  
Lipid Lowering ◽  
Hiv Protease Inhibitors ◽  
Kidney Transplant Recipients

Background. Functional abnormalities of high-density lipoprotein (HDL) could contribute to cardiovascular disease in chronic kidney disease patients. We measured a validated marker of HDL dysfunction, nitrated apolipoprotein A-I, in kidney transplant recipients to test the hypothesis that a functioning kidney transplant reduces serum nitrated apoA-I concentrations.Methods. Concentrations of nitrated apoA-I and apoB were measured using indirect sandwich ELISA assays on sera collected from each transplant subject before transplantation and at 1, 3, and 12 months after transplantation. Patients were excluded if they have history of diabetes, treatment with lipid-lowering medications or HIV protease inhibitors, prednisone dose > 15 mg/day, nephrotic range proteinuria, serum creatinine > 1.5 mg/dL, or active inflammatory disease. Sera from 18 transplanted patients were analyzed. Four subjects were excluded due to insufficient data. Twelve and eight patients had creatinine < 1.5 mg/dL at 3 and 12 months after transplantation, respectively.Results. Nitrated apoA-I was significantly reduced at 12 months after transplantation (p=0.039). The decrease in apoA-I nitration was associated with significant reduction in myeloperoxidase (MPO) activity (p=0.047). In contrast to apoA-I, nitrated apoB was not affected after kidney transplantation.Conclusions. Patients with well-functioning grafts had significant reduction in nitrated apoA-I 12 months after kidney transplantation. Further studies are needed in a large cohort to determine if nitrated apoA-I can be used as a valuable marker for cardiovascular risk stratification in chronic kidney disease.

scholarly journals Clinical Applications of Genetic Discoveries in Kidney Transplantation: a Review

Kidney360 ◽  
2020 ◽  
Vol 1 (4) ◽  
pp. 300-305
Author(s):  
Ethan P. Marin ◽  
Elizabeth Cohen ◽  
Neera Dahl
Keyword(s):  
Kidney Transplantation ◽  
Genetic Testing ◽  
Kidney Disease ◽  
Kidney Transplant ◽  
Clinical Applications ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients

Growth in knowledge of the genetics of kidney disease has revealed that significant percentages of patients with diverse types of nephropathy have causative mutations. Genetic testing is poised to play an increasing role in the care of patients with kidney disease. The role of genetic testing in kidney transplantation is not well established. This review will explore the ways in which genetic testing may be applied to improve the care of kidney transplant recipients and donors.

scholarly journals P0004REDUCED EXPRESSION OF PROXIMAL ACID-BASE TRANSPORT PROTEINS IN KIDNEY TRANSPLANT PATIENTS WITH METABOLIC ACIDOSIS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Anna Wiegand ◽  
Arezoo Daryadel ◽  
Pedro Henrique Imenez da Silva ◽  
Ariana Gaspert ◽  
Rudolf Peter Wuthrich ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Metabolic Acidosis ◽  
Kidney Disease ◽  
Proximal Tubule ◽  
Kidney Transplant ◽  
Transport Proteins ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Acid Base ◽  
Alkali Therapy

Abstract Background and Aims Metabolic acidosis (MA) is a frequent complication of chronic kidney disease and an independent risk factor for kidney disease progression and mortality. MA is highly prevalent after kidney transplantation (12%-58%)(1). However, there are scarcely any data available on the underlying pathomechanisms and in particular molecular mechanisms involved in metabolic acidosis after kidney transplantation. Thus, we wanted to investigate the expression of key acid base transport proteins in kidney biopsies of kidney transplant recipients with and without metabolic acidosis. Method We evaluated 22 kidney transplant biopsies including 9 biopsies from kidney transplant recipients (KTR) with MA, nine biopsies from KTRs without MA (control) and four biopsies from KTRs with MA that were consequently subjected to alkali therapy (Alkali therapy). Immunofluorescence staining was used to identify key renal acid-base transport proteins. Additionally, six control kidneys were analyzed. Immunofluorescence staining was used to identify key renal acid-base transport proteins along the nephron. In addition, RNA extraction and full RNA sequencing analysis of all biopsies –where available- was performed. Results In the proximal tubule, we observed reduced immunostaining for the sodium bicarbonate cotransporter NBCe1 (SLC4A4) in the MA group compared to the control and alkali group, whereas the alkali group demonstrated the strongest staining of all three groups. In the distal nephron, expression of the chloride/bicarbonate exchanger Pendrin (SLC26A4) and the B1 subunit of the V-ATPase (ATP6V1B1) were markedly stronger in the alkali and control group compared to the MA group. Expression of other acid base proteins such as Renal ammonia transporter RhCG (SLC42A3), Carbonic Anhydrase II, Glutamate dehydrogenase, anion exchanger AE1 (SLC4A1) and the B2 subunit of the V-ATPase (ATP6V1B2) showed no difference among all groups. Interestingly, the B2 subunit was absent in the proximal tubule in transplant biopsies of all groups. In kidney biopsies of transplant recipients with metabolic acidosis RNA abundance of NBCe1, CAII and Pendrin was lower while RhCG and B1 RNA counts were not different when compared to recipients without metabolic acidosis. Conclusion Our data demonstrate altered protein and mRNA expression of several key acid base transporters in kidney biopsies of transplant recipients with metabolic acidosis. Treatment with alkali may have the potential to reverse or prevent these changes in renal allografts after transplantation.

scholarly journals Antibody Response to mRNA Vaccines against SARS-CoV-2 with Chronic Kidney Disease, Hemodialysis, and after Kidney Transplantation

2021 ◽  
Vol 11 (1) ◽  
pp. 148
Author(s):  
Lukas Buchwinkler ◽  
Claire Anne Solagna ◽  
Janosch Messner ◽  
Markus Pirklbauer ◽  
Michael Rudnicki ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Transplantation ◽  
Kidney Disease ◽  
Antibody Response ◽  
Kidney Transplant ◽  
Mycophenolic Acid ◽  
Calcineurin Inhibitors ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Factors Associated

Most trials on mRNA vaccines against SARS-CoV-2 did not include patients with chronic kidney disease (CKD), hemodialysis (HD) patients, or kidney transplant recipients (KTR). However, those patients have a higher risk for a severe course of COVID-19 disease and mortality. Available literature has demonstrated a reduced efficacy of mRNA vaccines in HD patients and KTR, while data on CKD patients is scarce. Additionally, factors associated with non-response are poorly understood and not well characterized. We assessed antibody (AB) response (n = 582, 160 CKD patients, 206 patients on HD, 216 KTR) after the administration of two doses of a mRNA-vaccine with either BNT162b2 or mRNA-1273. AB measurements were carried out after a median of 91 days after first vaccinations, demonstrating non-response in 12.5% of CKD patients, 12.1% of HD patients, and 50% of KTR. AB titers were significantly higher in CKD patients than in HD patients or KTR. Factors associated with non-response were treated with rituximab in CKD patients, the use of calcineurin inhibitors in HD patients and older age, and the use of BNT162b2, mycophenolic acid, or glucocorticoids and lower hemoglobin levels in KTR. This study contributes to the understanding of the extent and conditions that predispose for non-response in patients with impaired kidney function.

scholarly journals Hepatitis C Treatment in Chronic Kidney Disease Patients: The Kidney Disease Improving Global Outcomes Perspective

2017 ◽  
Vol 43 (1-3) ◽  
pp. 206-209 ◽  
Author(s):  
Michel Jadoul ◽  
Paul Martin
Keyword(s):  
Chronic Kidney Disease ◽  
Hepatitis C ◽  
Kidney Disease ◽  
Kidney Transplant ◽  
Journal Club ◽  
Sustained Viral Response ◽  
Case Series ◽  
Calcineurin Inhibitors ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients

Background: Hepatitis C virus (HCV) infection is a very common infection found among hemodialysis (HD) and kidney transplant patients. It is associated with substantial morbidity and mortality. Direct-acting antiviral agents (DAAs) have much better efficacy (sustained viral response (SVR)) and tolerance than interferon-based regimens. Very recent studies extend this breakthrough finding to chronic kidney disease (CKD) populations. Summary: CKD patients with an estimated glomerular filtration rate (eGFR) >30 ml/min/1.73 m2 can be treated with any licensed DAA regimen. In CKD stages 4-5 (mostly HD), the combination of grazoprevir (100 mg) and elbasvir (50 mg), a once-daily oral regimen active against genotypes 1 and 4, induced in a very recent RCT an SVR rate >95%, with tolerance similar to that of placebo. Case series suggest that other DAA regimens are also very effective and well tolerated in HD patients. In kidney transplant recipients, 2 case series have reported 100% SVR with good tolerance of sofosbuvir-based regimens. Importantly, there is a risk of drug-drug interaction of several DAAs including calcineurin inhibitors. Finally, the availability of HCV+ grafts may markedly shorten the waiting time for transplantation. Key Messages: (1) In patients with an eGFR >30, all licensed DAAs regimens can be used. (2) Cure of HCV appears at hand in CKD stages 4-5, including dialysis patients, and in kidney transplant recipients. (3) The choice of DAA regimen in CKD should be based on HCV genotype, viral load, eGFR, concomitant medications, transplant candidacy and comorbidities. (4) The timing of treatment in potential kidney transplantation candidates (before versus after transplantation) should be decided in collaboration with the transplant center. Video Journal Club ‘Cappuccino with Claudio Ronco' at http://www.karger.com/?doi=452730.

scholarly journals Lifestyle, Inflammation, and Vascular Calcification in Kidney Transplant Recipients: Perspectives on Long-Term Outcomes

2020 ◽  
Vol 9 (6) ◽  
pp. 1911 ◽  
Author(s):  
Camilo G. Sotomayor ◽  
Charlotte A. te Velde-Keyzer ◽  
Martin H. de Borst ◽  
Gerjan J. Navis ◽  
Stephan J.L. Bakker
Keyword(s):  
Risk Factors ◽  
Kidney Transplantation ◽  
Kidney Disease ◽  
Kidney Transplant ◽  
Vascular Calcification ◽  
Graft Failure ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Long Term Outcomes

After decades of pioneering and improvement, kidney transplantation is now the renal replacement therapy of choice for most patients with end-stage kidney disease (ESKD). Where focus has traditionally been on surgical techniques and immunosuppressive treatment with prevention of rejection and infection in relation to short-term outcomes, nowadays, so many people are long-living with a transplanted kidney that lifestyle, including diet and exposure to toxic contaminants, also becomes of importance for the kidney transplantation field. Beyond hazards of immunological nature, a systematic assessment of potentially modifiable—yet rather overlooked—risk factors for late graft failure and excess cardiovascular risk may reveal novel targets for clinical intervention to optimize long-term health and downturn current rates of premature death of kidney transplant recipients (KTR). It should also be realized that while kidney transplantation aims to restore kidney function, it incompletely mitigates mechanisms of disease such as chronic low-grade inflammation with persistent redox imbalance and deregulated mineral and bone metabolism. While the vicious circle between inflammation and oxidative stress as common final pathway of a multitude of insults plays an established pathological role in native chronic kidney disease, its characterization post-kidney transplant remains less than satisfactory. Next to chronic inflammatory status, markedly accelerated vascular calcification persists after kidney transplantation and is likewise suggested a major independent mechanism, whose mitigation may counterbalance the excess risk of cardiovascular disease post-kidney transplant. Hereby, we first discuss modifiable dietary elements and toxic environmental contaminants that may explain increased risk of cardiovascular mortality and late graft failure in KTR. Next, we specify laboratory and clinical readouts, with a postulated role within persisting mechanisms of disease post-kidney transplantation (i.e., inflammation and redox imbalance and vascular calcification), as potential non-traditional risk factors for adverse long-term outcomes in KTR. Reflection on these current research opportunities is warranted among the research and clinical kidney transplantation community.

scholarly journals Current Pharmacological Intervention and Medical Management for Diabetic Kidney Transplant Recipients

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 413
Author(s):  
Theerawut Klangjareonchai ◽  
Natsuki Eguchi ◽  
Ekamol Tantisattamo ◽  
Antoney J. Ferrey ◽  
Uttam Reddy ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Kidney Transplantation ◽  
Kidney Transplant ◽  
Pharmacological Intervention ◽  
Diabetic Patients ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Kidney Allograft ◽  
Post Transplant ◽  
Glucose Management

Hyperglycemia after kidney transplantation is common in both diabetic and non-diabetic patients. Both pretransplant and post-transplant diabetes mellitus are associated with increased kidney allograft failure and mortality. Glucose management may be challenging for kidney transplant recipients. The pathophysiology and pattern of hyperglycemia in patients following kidney transplantation is different from those with type 2 diabetes mellitus. In patients with pre-existing and post-transplant diabetes mellitus, there is limited data on the management of hyperglycemia after kidney transplantation. The following article discusses the nomenclature and diagnosis of pre- and post-transplant diabetes mellitus, the impact of transplant-related hyperglycemia on patient and kidney allograft outcomes, risk factors and potential pathogenic mechanisms of hyperglycemia after kidney transplantation, glucose management before and after transplantation, and modalities for prevention of post-transplant diabetes mellitus.

scholarly journals 530. COVID-19 in kidney transplant recipients: Single-center experience and case-control study

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S332-S332
Author(s):  
Anna Hardesty ◽  
Aakriti Pandita ◽  
Yiyun Shi ◽  
Kendra Vieira ◽  
Ralph Rogers ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Case Control Study ◽  
Clinical Course ◽  
Case Series ◽  
Case Fatality ◽  
Case Control ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Transplant Patients ◽  
Control Study

Abstract Background Organ transplant recipients (OTR) are considered high-risk for morbidity and mortality from COVID-19. Case-fatality rates (CFR) vary significantly in different case series, and some patients were still hospitalized at the time of analyses. To our knowledge, no case-control study of COVID-19 in OTR has been published to-date. Methods We captured kidney transplant recipients (KTR) diagnosed with COVID-19 between 3/1 and 5/18/2020. After exclusion of KTR on hemodialysis and off immunosuppression (IS), we compared the clinical course of COVID-19 between hospitalized KTR and non-transplant patients, matched by sex and age (controls). All patients were discharged from the hospital or died. Results 16 KTR had COVID-19. All 3 KTR off IS, who were excluded from further analyses, survived. Median age was 54 (range: 34–65) years; 5/13 KTR (38.4%) were men. Median time from transplant was 41 (range: 1–203) months. Two KTR, both transplanted &gt;10 years ago, were managed as outpatients. IS was reduced in 12/13 (92.3%), most often by discontinuation of the antimetabolite. IL6 levels were &gt;1,000 (normal: &lt; 5) pg/mL in 3 KTR. Tacrolimus or sirolimus levels were &gt;10 ng/mL in 6/9 KTR (67%) (Table 1). Eleven KTR were hospitalized (84.6%) and matched with 44 controls. One KTR, the only one treated with hydroxychloroquine, died (CFR 5.8%; 7.6% in KTR on IS; 9% in hospitalized KTR on IS). Four controls died (CFR: 9%; state CFR: 5.2%; inpatient CFR: 16.6%). There were no significant differences in length of stay or worst oxygenation status between hospitalized KTR and controls. Four KTR (30.7%), received remdesivir, 4 convalescent plasma, 3 (23%) tocilizumab. KTR received more often broad-spectrum antibiotics, convalescent plasma or tocilizumab, compared to controls (Table 2). Table 1 Table 2 Conclusion Unlike early reports from the pandemic epicenters, the clinical course and outcomes of KTR with COVID-19 in our small case series were comparable to those of non-transplant patients. Calcineurin or mTOR inhibitor levels were high, likely due to diarrhea and COVID-19-related hepatic dysfunction. Extremely high IL6 levels were common. The role of IS and potential benefits from investigational treatments remain to be elucidated. A larger multi-institutional study is underway. Disclosures All Authors: No reported disclosures

scholarly journals Circulating endothelial cells transiently increase in peripheral blood after kidney transplantation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
H. Tejeda-Mora ◽  
J. G. H. P. Verhoeven ◽  
W. Verschoor ◽  
K. Boer ◽  
D. A. Hesselink ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Kidney Transplantation ◽  
Kidney Transplant ◽  
Allograft Rejection ◽  
Flow Cytometric Analysis ◽  
Principal Component ◽  
Circulating Endothelial Cells ◽  
Clinical Markers ◽  
Kidney Transplant Recipients ◽  
Post Transplant

AbstractThe diagnosis of kidney allograft rejection is based on late histological and clinical markers. Early, specific and minimally-invasive biomarkers may improve rejection diagnosis. Endothelial cells (EC) are one of the earliest targets in kidney transplant rejection. We investigated whether circulating EC (cEC) could serve as an earlier and less invasive biomarker for allograft rejection. Blood was collected from a cohort of 51 kidney transplant recipients before and at multiple timepoints after transplantation, including during a for cause biopsy. The number and phenotype of EC was assessed by flow-cytometric analysis. Unbiased selection of EC was done using principal component (PCA) analysis. Paired analysis revealed a transient cEC increase of 2.1-fold on the third day post-transplant, recovering to preoperative levels at seventh day post-transplant and onwards. Analysis of HLA subtype demonstrated that cEC mainly originate from the recipient. cEC levels were not associated with allograft rejection, allograft function or other allograft pathologies. However, cEC in patients with allograft rejection and increased levels of cEC showed elevated levels of KIM-1 (kidney injury marker-1). These findings indicate that cEC numbers and phenotype are affected after kidney transplantation but may not improve rejection diagnosis.

Sign in / Sign up

Export Citation Format

Share Document