| Literature DB >> 33077702 |
Monika Wieliczko1, Urszula Ołdakowska-Jedynak1, Jolanta Małyszko1.
Abstract
Chronic kidney disease (CKD) has been recognized as an increasingly common complication of liver transplantation (OLTx). Post-transplant renal dysfunction contributes to long-term morbidity and mortality following OLTx and is a very important issue in the management of liver transplant recipients. Its etiology is multifactorial and can be determined by kidney biopsy, which is too rarely done in this patient group. In the clinical context of patients with liver cirrhosis, accurate and reliable evaluation of the renal injury is crucial. We performed a review of kidney biopsies in patients with symptoms of CKD (proteinuria/hematuria/elevated creatinine) before and after liver transplantation in the published literature. Kidney biopsies were performed either before or after liver transplantation using percutaneous technique. There are few reports on transjugular kidney biopsy. Biopsy results prevented unnecessary modification of immunosuppressive therapy or selection of candidates for liver transplantation. In our opinion, kidney biopsy is a clinically relevant diagnostic approach to recognize kidney disease before and after liver transplantation, it also helps with the management of kidney disease in this population, and it is safe. Kidney biopsy should be offered more often in liver transplant patients to ensure appropriate therapy in concomitant CKD in this population. Our decisions today will impact clinical outcomes in the future.Entities:
Year: 2020 PMID: 33077702 PMCID: PMC7587156 DOI: 10.12659/AOT.925891
Source DB: PubMed Journal: Ann Transplant ISSN: 1425-9524 Impact factor: 1.530
Kidney biopsy before liver transplantation.
| First author/reference number/study period | Number of patients | The most common causes of ESLD | Renal biopsy indication | Renal biopsy results | Clinical implication |
|---|---|---|---|---|---|
| Axelsen et al. [ | 23 | PSC/PBC | Scr 80–180 μmol/L | Minor glomerular abnormalities n=9 | All biopsies showed glomerular abnormalities, which may contribute to the occurrence of post-transplant renal dysfunction. |
| McGuire et al. [ | 30 | HCV | NA | 25 patients had immune-complex glomerulonephritis: | Immune-complex glomerulonephritis was common in patients with end-stage HCV-induced cirrhosis and was often clinically silent. |
| Wadei et al. [ | 44 | HCV | GFR <40 mL/min (n=37), proteinuria and/or hematuria | IgAN n=20 | Renal biopsy is feasible in liver transplant candidates with moderate to severe renal failure and provides histological data that does not relate to the pretransplant clinical data. |
| Calmus et al. [ | 60 | ALD | Unselected patient with ESLD undergoing screening for LTx | 25 pts had a morphological diagnosis of renal disease: | In patients with ESLD, IgA nephropathy and diabetic lesions were frequently found despite the absence of renal impairment and/or urinalysis abnormalities. |
| Pichler et al. [ | 59 | HCV | Liver transplant candidate with renal impairment of unclear etiology referred for SLK | MPGN 23% patients | Renal biopsy can be relatively safe in this high-risk population, may help diagnose the etiology of renal disease, may predict post-transplant kidney function, and can be useful in kidney allocation for liver transplant candidates. |
| Singh et al. [ | 11 | HCV | Liver transplant candidate with renal impairment of unclear etiology referred for SLK | Minimal changes n=8 | LTx n=8 |
| Wadei et al. [ | 128 | HCV | Liver transplant candidate with renal impairment of unclear etiology referred for SLK | Normal n=13 | MELD score, serum creatinine, urinary sodium excretion, and renal size did not correlate with biopsy diagnosis; only SBP at the time of LTx evaluation correlates with renal histology. |
AKI – acute kidney injury; ATN – acute tubular necrosis; CKD – chronic kidney disease; CNI – calcineurin inhibitor; CsA – cyclosporine A; DM – diabetes mellitus; DN – diabetic nephropathy; ESLD – end-stage liver disease; FSGS – focal segmental glomerulosclerosis; GN – glomerulonephritis; GS – glomerulosclerosis; HGS – hepatic glomerulosclerosis; HP – hypertension; iGFR – iothalamate glomerular filtration rate; IF – interstitial fibrosis; IgA – immunoglobulin A; HBV – hepatitis B virus; HCV – hepatitis C virus; ALD – alcoholic liver disease; IFTA – interstitial fibrosis and tubular atrophy; LAT – alone liver transplantation, LTx liver transplantation; MGA – minor glomerular abnormalities; MPGN – membranoproliferative glomerulonephritis; NA – not available; NALD – nonalcoholic liver disease; NASH – nonalcoholic steatohepatitis; NRSOT – nonrenal solid organ transplantation; PSC – primary sclerosing cholangitis; RB – renal biopsy; RRT – renal replacement therapy; SBP – systolic blood pressure; SLK – tx simultaneous-liver-kidney transplantation; TA – tubular atrophy; TAC – tacrolimus; TMA – thrombotic microangiopathy; TDV tenofovir associated nephrotoxicity.
Figure 1Indications for kidney biopsy after liver transplantation and a short algorithm. (AKI/CKD “unknown” after exclusion: dehydration, renal arterial stenosis/thrombosis, kidney infection, heart failure, CNI overdosage, rhabdomyolysis, use of nephrotoxic drugs).
Kidney biopsy after liver transplantation.
| First author/reference number/ study period | The mean time until biopsy after LTx | Number of patients | The most common causes of ESLD | Renal biopsy indication | Renal biopsy results | Clinical implication |
|---|---|---|---|---|---|---|
| Neau-Cransac et al. [ | 72 (1–108) months | 9 | ALD | Scr >200 μmol/L | Chronic CNI-related nephrotoxicity | Cyclosporine and tacrolimus withdrawal. Despite this modification, there was no significant renal function improvement. |
| Pillebout et al. [ | 4.8 years (0.5–11.6) | 26 | HCV | CKD | 45±3% of sclerotic glomeruli | CKD in LTx recipients is more complex than originally thought histologic lesions suggesting the interplay of multiple factors in renal destruction and should not be classified as anti-calcineurin nephrotoxicity without further investigations, including renal histology. |
| Kim et al. [ | 4.89 years | 81 | HCV | Scr ≥1.5 mgdl or new proteinuria | Arterionephrosclerosis: mild n=61 | All biopsies demonstrated universal glomerular abnormalities in kidney biopsies after LTx. |
| Kamar et al. [ | 60±48 months | 99 | HCV | eGFR ≥15 ml/min. | Only 5 patients had features of a specific kidney disease: IgA nephropathy, cryoglobulinemic membranoproliferative glomerulonephritis, nephroangiosclerosis, signs of TMA, and tubulointerstitial nephritis. | In the setting of liver transplantation, this is the largest kidney-histology study to confirm that histological kidney lesions are complex, multiple, and interrelated. 13 pts converted from CNIs to rapamycin but with no significant improvement in eGFR. Kidney function at 6 months post-transplant can predict long-term kidney function and histology. |
| Kubal et al. [ | 4years (0.3–15.9) | 62 NRSOT | NA | Liver, heart, lung, and heart-lung transplant recipients who underwent a renal biopsy at least 3 months post-transplant as a part of work up for deteriorating renal function. | 35.5% CNI chronic nephrotoxicity (50% also hypertensive nephropathy). | Many patients do not have overt histological evidence of CNI toxicity. Quantitative parameters of chronic damage can stratify renal prognosis. |
| Lee JH et al. [ | 24.5 months (3–66) | 10 | HBV | Unexplained increase of serum creatinine, newly developed proteinuria with microscopic hematuria. | IgA GN (4); | Kidney biopsy is safe and effective method after LTx. Management of patients based on the result of kidney biopsy can improve renal outcome. |
| Chan et al. [ | 1590 days (102–3699) | 10 | HBV | Proteinuria (>1 g/24h) (in 7 pts in the nephrotic range) or >20% increase in serum creatine level from baseline on at least 2 occasions. | DN n=6 | Most biopsies showed complex renal lesions while CNI nephrotoxicity was rare. |
| Fujinaga et al. [ | 20–76 months | 4 | HCV | Regardless of serum creatinine level, unexplained progressive renal failure, proteinuria, persistent glomerular hematuria and systemic disease with renal involvement. | Only one patient had HCV related membranous proliferative nephritis, DN n=1 | Although HCV and hypertension were determined to be independent risk factors for late renal disease, a renal biopsy should be performed when clinical symptoms develop regardless of creatinine levels to provide appropriate treatment. |
| Welker et al. [ | 3 years (0.2–12) | 14 | HCV | Severe renal impairment with progressive deterioration of renal function, overt proteinuria | IgA GN n=4 | Renal biopsy in patients with CKD after LTx seems safe and may offer specific therapeutic options. |
| Tsapenko et al. [ | 6.9 years (4.6 months – 16.2 years) | 23/1698 (23 RB from 1698 pts after OLTx) | Different | Proteinuria, progressive CKD, hematuria | Focal and global GS n=8 (30.4%) | Immunosuppression was modified in 8 pts; |
| Lee JP et al. [ | NA | 9/431 | HBV (80%) | Proteinuria >1g/d, Persistent microscopic hematuria, Progressive deterioration of renal function. | Global GS n=9 (100%; 3.7–93.5%) | CNI withdrawal in 7 pts with improvement of kidney function; |
| Schwartz et al. [ | 35 months | 39 (41 biopsies) | HBV | AKI n=5 (12%) | IgAN n=6 | CNI terminated in TMA and CNI toxicity. |
| Hiesse et al. [ | NA | 9 | NA | Significant proteinuria | MPGN with immunodeposits n=4 | All underwent liver transplantation followed by kidney transplantation. |
AKI – acute kidney injury; ATN – acute tubular necrosis; CKD – chronic kidney disease; CNI – calcineurin inhibitor; CsA – cyclosporine A; DM – diabetes mellitus; DN – diabetic nephropathy; ESLD – end-stage liver disease; FSGS – focal segmental glomerulosclerosis; GN – glomerulonephritis; GS glomerulosclerosis; HCC – hepatocellular carcinoma; HGS – hepatic glomerulosclerosis; HP – hypertension IF interstitial fibrosis; IgA - immunoglobulin A; HBV – hepatitis B virus; HCV – hepatitis C virus; ALD – alcoholic liver disease; IFTA – interstitial fibrosis and tubular atrophy; LAT – alone liver transplantation, LTx – liver transplantation; MGA – minor glomerular abnormalities; MPGN – membranoproliferative glomerulonephritis; NA – not available; NASH – nonalcoholic steatohepatitis, NRSOT – nonrenal solid organ transplantation; RAAS – renin-angiotensin-aldosterone system; RB – renal biopsy; RRT – renal replacement therapy; SLK – tx simultaneous-liver-kidney transplantation; TA – tubular atrophy; TAC – tacrolimus; TMA – thrombotic microangiopathy; TDV – tenofovir-associated nephrotoxicity.
Transjugular kidney biopsy in liver transplant recipients.
| First author/reference number/study period | Number of patients | The most common causes of ESLD | Renal biopsy indication | Renal biopsy results | Clinical implication |
|---|---|---|---|---|---|
| Jouet et al. [ | 55 | ALD | Patients considered for LTx | Glomerular lesions Interstitial abnormalities | The transjugular biopsy may be a useful procedure in patients with cirrhosis and clotting disorders. This approach may influence treatment decisions in patients proposed for liver transplantation. |
| Sam et al. [ | 29 | No data | Tubular injury MPGN | Irrespective of urine or blood findings, glomerular, and tubular abnormalities are relatively common in the setting of advanced liver disease. | |
| Abbott et al. [ | 9 | No data | – | Transjugular biopsy appears to be efficacious in high-risk patients for whom percutaneous procedure is contraindicated. |
AKI – acute kidney injury; ATN – acute tubular necrosis; CKD – chronic kidney disease; CNI – calcineurin inhibitor; CsA – cyclosporine A; DM – diabetes mellitus; DN – diabetic nephropathy; ESLD – end-stage liver disease; FSGS – focal segmental glomerulosclerosis; GN – glomerulonephritis; GS – glomerulosclerosis; HGS – hepatic glomerulosclerosis; HP – hypertension IF interstitial fibrosis; IgA – immunoglobulin A; HBV – hepatitis B virus; HCV – hepatitis C virus; ALD – alcoholic liver disease; IFTA – interstitial fibrosis and tubular atrophy; LAT – alone liver transplantation; LTx – liver transplantation; MGA – minor glomerular abnormalities; MPGN – membranoproliferative glomerulonephritis; NA – not available; NASH – nonalcoholic steatohepatitis; NRSOT – nonrenal solid organ transplantation; RB – renal biopsy; RRT – renal replacement therapy; SLK – tx simultaneous-liver-kidney transplantation; TA – tubular atrophy; TAC – tacrolimus; TMA – thrombotic microangiopathy; TDV – tenofovir-associated nephrotoxicity.