Liver Cirrhosis With Chronic Kidney Disease

Currently, data on the prevalence, clinical impact, and treatment modalities of cirrhosis with chronic kidney disease (CKD) remain scarce. But the incidence of CKD in patients with cirrhosis has risen dramatically over the past decade. The main reason for the increase in CKD prevalence appears to be the growing awareness of the disease, as well as the rising prevalence of diabetes mellitus (DM), hypertension, and nonalcoholic fatty liver disease (NAFLD).

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This review provides a detailed overview of CKD in cirrhosis, including its clinical impact and the difficulties clinicians may face in diagnosis and treatment.

Definition and classification of liver cirrhosis with CKD

Cirrhosis with CKD is currently defined as a decrease in estimated glomerular filtration rate (eGFR) to <60 mL/min for more than 3 months, as calculated by the Modified Diet in Renal Disease (MDRD)-6 formula. Currently, the diagnosis of CKD does not require conclusive evidence of renal impairment, such as proteinuria, hematuria, renal imaging, or pathological abnormalities.

Improving Kidney Outcomes Worldwide has divided CKD into structural and functional categories based on the presence or absence of kidney damage. Patients with liver cirrhosis may have some risk factors for structural CKD, such as DM, NAFLD, and atherosclerosis. In addition, sustained renal vasoconstriction in functional CKD can lead to structural changes that transform it into structural CKD.

Clinical impact of liver cirrhosis complicated with CKD

CKD can affect the clinical presentation, complications, treatment strategies, and outcomes of patients with cirrhosis in multiple ways.

In patients with cirrhosis, CKD may lead to ascites and edema through various means, such as nephrogenic ascites, chronic fluid overload, hypoproteinemia, and cardiomyopathy. Patients with concurrent hepatic and renal insufficiency may have a higher tendency to bleed due to multiple complex hemostatic abnormalities. CKD is an independent risk factor for cardiovascular death and can aggravate anemia caused by cirrhosis.

Both CKD and cirrhosis cause immunosuppression, leading to an increased risk of infection. Patients with cirrhosis and CKD appear to be at increased risk of malignancy. After adjusting for many possible confounders, lower GFR has been shown to be independently associated with an increased risk of renal cell carcinoma and urothelial carcinoma. CKD is associated with increased mortality from the liver, kidney, and urothelial cancers.

Because liver and kidney disease can independently cause anorexia, anemia, ascites, bleeding tendency, and encephalopathy, it is often difficult to determine which disease is responsible for these symptoms in patients with cirrhosis and CKD. This can make it difficult to determine optimal treatment options, such as the need for renal replacement therapy.

Cirrhosis with CKD is associated with an increased frequency of adverse outcomes and complications. Wong et al found that compared with cirrhotic patients without CKD, patients with cirrhosis and CKD had a higher incidence of acute kidney injury (AKI), need for dialysis, and 30-day mortality. A study by Bassegoda et al showed that compared with patients without CKD, patients with cirrhosis and CKD had a higher incidence of AKI, refractory ascites, bacterial infection, and need for liver transplantation (LT). Furthermore, cirrhosis is independently associated with poor outcomes in CKD patients.

Diagnosis and evaluation of liver cirrhosis complicated with CKD

The diagnosis of cirrhosis with CKD is based on GFR (the expert panel recommends using MDRD-6 to assess eGFR). Abnormal urinalysis and/or renal ultrasonography findings are often seen in advanced CKD and therefore do not require a diagnosis. In patients with CKD, cirrhosis can be diagnosed by histopathology or liver ultrasonography, as well as clinical manifestations of portal hypertension and/or hepatic decompensation.

The most widely used biomarker for assessing renal injury in patients with cirrhosis is urinary neutrophil gelatinase-associated lipocalin (uNGAL), an inflammatory biomarker produced by damaged renal tubular cells. uNGAL was positively correlated with the severity of renal impairment in CKD patients, suggesting its prognostic significance in CKD. However, the prognostic value of uNGAL in patients with cirrhosis and CKD is unclear.

Renal duplex Doppler ultrasonography is a simple, noninvasive, and highly effective method that can be used in patients with cirrhosis to study intrarenal hemodynamics. A test that assesses renal vascular resistance as a marker of vasoconstriction, the renal resistance index (RRI) can be used to detect early renal insufficiency in patients with cirrhosis.

Treatment of liver cirrhosis with CKD

Treatment of cirrhosis with CKD presents many challenges, especially in controlling the flow of ascites and edema. Diuretic therapy has several limitations. Patients with functional CKD are generally not treated with diuretics because they may further aggravate renal failure by causing intravascular volume loss and may induce electrolyte imbalance.

Diuretics appear to be useful in the management of ascites and edema in patients with structural CKD. Still, CKD patients often have varying degrees of diuretic resistance, thus requiring higher doses of diuretics to overcome. Vasopressin 2 receptor antagonist Vaptan may be considered for the treatment of patients with liver cirrhosis and CKD who are intolerant or poorly responding to diuretics.

Current guidelines mostly do not recommend using vasoconstrictor therapy in functional CKD.

Transjugular intrahepatic portosystemic shunt (TIPS) reduces portal pressure, improves renal function, and reduces ascites. TIPS appears to be very effective in patients with functional CKD, and limited data suggest that it is also effective in structural CKD. However, TIPS may increase the incidence of hepatic encephalopathy (HE), so patients with encephalopathy, cardiopulmonary disease, and severe liver dysfunction should avoid using TIPS.

Because assessment of renal function in patients with advanced cirrhosis can be difficult, renal biopsy should be considered whenever possible to determine renal parenchymal changes and to decide whether to proceed with LT or combined liver-kidney transplantation (SLKT). SLKT should be considered in patients with low eGFR and renal biopsy showing >30% glomerulosclerosis and/or interstitial fibrosis.

for more information: Ali.ma@wecistanche.com