20 October 2020: Review Paper
Clinical Relevance of Kidney Biopsy in Patients Qualified for Liver Transplantation and After This Procedure in the Model for End-stage Liver Disease (MELD) Era: Where Are We Today?
Monika Wieliczko ABCDEF , Urszula Ołdakowska-Jedynak BCEF , Jolanta Małyszko ABCDEFG*DOI: 10.12659/AOT.925891
Ann Transplant 2020; 25:e925891
Table 2 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. [] 1989–200033 | 72 (1–108) months | 9 | ALDHCV | 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. [] 1999–200328 | 4.8 years (0.5–11.6) | 26 | HCVALD | CKDIsolated proteinuria 1.2 g/24 h | 45±3% of sclerotic glomeruli45±4%, associated with marked vascular lesions n=17TMA n=13;CNI nephrotoxicity n=12DKD n=9FSGS n=9 | 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. [] 2002–200834 | 4.89 years | 81 | HCV | Scr ≥1.5 mgdl or new proteinuria | Arterionephrosclerosis: mild n=61moderate n=20Tubulointerstitial abnormalities n=53, mild tubular atrophy n=45Podocyte effacement n=65GBM widening n=52HGS n=30FSGS n=21CNI toxicity n=13 | All biopsies demonstrated universal glomerular abnormalities in kidney biopsies after LTx.Only 16% showed evidence of CNI toxicity. |
| Kamar et al. [] 2006–200735 | 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. [] Since 199936 | 4years (0.3–15.9) | 62 NRSOT31 pts post LTx | 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).Of the remaining 40 biopsies, 27 showed HN with no or minimal arteriolar hyalinosis, ATN (5), MPGN (2), DN (1), postinfectious GN (1), and membranous nephropathy (12) | Many patients do not have overt histological evidence of CNI toxicity. Quantitative parameters of chronic damage can stratify renal prognosis. |
| Lee JH et al. [] 1999–201227 | 24.5 months (3–66) | 10 | HBVALD | Unexplained increase of serum creatinine, newly developed proteinuria with microscopic hematuria. | IgA GN (4);Mesangial proliferative GN (1)CNI-induced nephrotoxicity (3)GS in 90% of cases; IF in 80% of casesTA in 80% of cases | 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. [] 2002–201037 | 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=6IgA GN n=4.Only one patient had chronic CNI− nephrotoxicity. | Most biopsies showed complex renal lesions while CNI nephrotoxicity was rare. |
| Fujinaga et al. [] 2002–200826 | 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=1Tacrolimus toxicity n=2. | 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. [] 2011–201531 | 3 years (0.2–12) | 14 | HCVALD | Severe renal impairment with progressive deterioration of renal function, overt proteinuria0.2–8.6 g/24 h | IgA GN n=4MPGN type I n=1 Membranous GN n=1Nephrosclerosis n=5TDF n=1DN/CNI toxicity n=1AA amyloidosis n=1IFTA was present in all biopsies ranging from 5–70% | Renal biopsy in patients with CKD after LTx seems safe and may offer specific therapeutic options.Unnecessary changes of immunosuppression can be avoided in a considerable number of patients. |
| Tsapenko et al. [] 1988–2008 (retrospective analysis)32 | 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%)FSGS n= 2 (8.7%)IgAN n=2 (8.7%)MPGN n=2 (8.7%)Nonspecific GN n=1 (4.3%)CNI toxicity n=2 (8.7%)DN n=2 (8.7%)ATN n=1 (4.3%)Nonspecific n=3 (13%) | Immunosuppression was modified in 8 pts;RAAS blockade was initiated in 6 pts; |
| Lee JP et al. [] 1997–2008 (retrospective analysis)39 | NA | 9/431 | HBV (80%)HCVHCC | Proteinuria >1g/d, Persistent microscopic hematuria, Progressive deterioration of renal function. | Global GS n=9 (100%; 3.7–93.5%)Segmental GS n=4 (44.4%)Fibrosis n=9 (100%)Arteriopathy 6 (66.7%)Arteriolopathy 8 (88.9%)DN n=0Chronic CNI toxicity n=0 | CNI withdrawal in 7 pts with improvement of kidney function;ARB addition in 2 pts. |
| Schwartz et al. [] 2009 (retrospective analysis); 105 KB in nonrenal transplant recipients)40 | 35 months | 39 (41 biopsies) | HBVHCVALDCystic fibrosisMalformation of the biliary duct | AKI n=5 (12%)Creatinine increases n=33 (80.5%)Heavy proteinuria n=12 (29.3%)Renal insufficiency before re-Tx n=3 (7.3%). | IgAN n=6Minimal changes n=1MPGN n=3TMA n=5Iron overload n=2CNI toxicity n=25 (64%)HP n=16 (41%)AT injury n=19 (49%) | CNI terminated in TMA and CNI toxicity. |
| Hiesse et al. [] 1990–199442 | NA | 9 | NA | Significant proteinuriaRenal function impairment | MPGN with immunodeposits n=4MN n=1DN n=2Interstitial nephritis n=2 | 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. | ||||||