Acute Pancreatitis in Chronic Kidney Disease—A Common but Often Misunderstood Combination

Abstract

The occurrence of pancreatitis has been reported among chronic kidney disease (CKD) patients, especially those who are on peritoneal dialysis. It contributes to an increased morbidity and mortality in patients who are already suffering from renal failure. The diagnosis of acute pancreatitis is also modified by the loss of renal function with altered levels of pancreatic enzyme estimation and the contribution of pancreatic damage due to uremia and dialysis. We describe two cases of CKD who presented with acute pancreatitis and also briefly review the literature.

• acute pancreatitis
• chronic kidney disease
• amylase
• lipase
• local hypercalcemia

INTRODUCTION

Acute pancreatitis is an acute inflammatory process involving the pancreas. It contributes significantly to the morbidity and mortality and also causes prolongation of hospital stay of patients. Chronic kidney disease (CKD) patients have additional risk factors compared to that of the general population and many mechanisms have been postulated.

CASE HISTORY

Case One

Fifty-year-old female patient was diagnosed to have CKD 3 years ago and was on hemodialysis (HD) for the last 6 months. The basic underlying renal disease was not clear. There is no history of alcohol intake, gall stone disease, any history suggestive of immunological diseases, or any history of drugs predisposing to pancreatitis. She presented with severe abdominal pain for the last 5 days which was radiating to the back along with nausea and vomiting and decreased urine output for the last 3 days to <400 mL/day. She was hemodynamically stable and examination revealed a tender ill-defined mass palpable over the epigastric region. Investigations revealed urea of 254 mg/dL, creatinine of 6.5 mg/dL, albumin of 2.1 mg/dL, hemoglobin of 7.4 g/dL, total leucocyte count (TLC) of 24,100/μL, triglyceride of 177 mg/dL, serum cholesterol of 64 mg/dL, PO₄ of 5.2 mg/dL, corrected calcium of 7.5 mg/dL, and liver function tests (LFT) of normal range. Serum amylase on admission was 4574 U/L and lipase was 3368 U/L. Ultrasound (USG) showed bulky pancreas with mild peripancreatic collection, no cholelithiasis or choledocholithiasis, and bilateral shrunken kidneys. There was no evidence of chronic pancreatitis or any anatomical anomalies in the pancreas. In view of the markedly raised pancreatic enzymes and ultrasound findings which were very evidently showing findings of acute pancreatitis, a computed tomography (CT) scan was not done. Moreover, we did not go ahead with a contrast enhanced computed tomography scan due to the presence of some residual renal function. She was managed conservatively and was discharged after 15 days of admission. The serum lipase on discharge was 59 U/L.

Case Two

A 54-year-old female patient with type 2 diabetes mellitus and diabetic nephropathy, in CKD stage IV for the last 3 years without any history suggestive of alcohol intake, gall stone disease or immunological diseases, or any drug intake predisposing to pancreatitis, presented with complaints of abdominal pain and nausea for the last 2 weeks. She was admitted in a private nursing home and was diagnosed to have pancreatitis and renal failure and was referred to us for further management. On examination there was mild epigastric tenderness and no mass was palpable per abdomen. Investigations revealed creatinine of 6.3 mg/dL, serum lipase of 928 U/L, amylase of 278 U/L, albumin of 2.3 mg/dL, calcium of 7.3 mg/dL (corrected calcium level of 8.7 mg/dL), triglyceride of 130 mg/dL, LFT of normal range, and TLC of 12,300/μL. USG showed small atrophic right kidney with hydronephrosis and enlarged right kidney with loss of corticomedullary differentiation, and the pancreas was not visualized. There was no evidence of gall stones. Doppler USG did not show any evidence of renal artery stenosis. Subsequently, a CT scan was done which revealed enlarged pancreas with peripancreatic fat stranding (Figure 1) and the absence of features suggestive of chronic pancreatitis or any other pancreatic anomalies which could predispose to acute pancreatitis. The serum lipase and amylase returned to normal after 7 days of admission along with clinical improvement. She was managed conservatively, initiated on HD and continues to be on HD for 2 months after discharge.

Figure 1.  Noncontrast CT scan of the abdomen showing bulky pancreas with peripancreatic fat stranding suggestive of grade C pancreatitis.

DISCUSSION

The occurrence of acute pancreatitis among patients with end-stage renal disease (ESRD) has been known for a long time, and it has been shown in studies that the prevalence of acute pancreatitis is high in patients who are on dialysis.¹ Autopsy studies have also shown that a significant proportion (up to 60%) of uremic patients on long-term HD have underlying pancreatic disease showing predominantly only histological changes as they did not correlate with the clinical picture.² The incidence of pancreatitis is significantly more in peritoneal dialysis (PD) patients (148–266/100,000/year) compared to 32–67/100,000/year in HD patients in whom the incidence is similar to the general population (5–80/100,000/year).^3,4 The morbidity and frequency of necrotizing pancreatitis are more in those on PD. The incidence of acute pancreatitis among patients with CKD not on HD is not clearly known. Abnormal exocrine pancreatic function has been found in 10–64% of patients with ESRD. This can contribute to malnutrition and diarrhea in this population.⁵

Even though the common etiological factors for pancreatitis contribute to many of the cases of CKD, the etiology of pancreatitis cannot be ascertained in more than half of the patients in whom the cause remains idiopathic.³ But, there are some factors that are specifically present in CKD patients, especially those who are on chronic dialysis [both HD and continuous ambulatory peritoneal dialysis (CAPD)]. High incidence of pancreatic anatomical abnormalities documented on postmortem examination; toxic substances in PD dialysate, bags, and tubing; alterations in serum calcium and parathyroid hormone; and bacterial and viral infections are some contributing factors.⁶ “Local hypercalcemia” in the pancreas due to calcium in the PD solution has also been postulated.⁷ Increase in various gastrointestinal hormones such as cholecystokinin, gastric inhibitory polypeptide, and glucagon in patients with CKD can stimulate hypersecretion of pancreatic enzymes such as trypsin which can contribute to impairment in pancreatic function.⁸ There is also this unique situation of coexistence of peritonitis and pancreatitis in patients who are on CAPD. This presents a diagnostic dilemma for the physician as the symptoms may overlap and both can result in elevation of serum amylase.

The clinical features of pancreatitis in patients with CKD are no different from those in the general population. The only exception being that of the coexistence of peritonitis and pancreatitis which is clinically difficult to differentiate. Serum amylase and lipase are traditionally used for the diagnosis of acute pancreatitis. Pancreatic enzymes are normally filtered by the kidneys to be reabsorbed at varying rates.⁹ In patients with renal failure, there are elevated levels of these pancreatic enzymes without the presence of acute pancreatitis. The cause of this elevation could be either due to the decreased renal clearance of these enzymes or due to the pancreatic damage due to the renal failure and dialysis. Royse et al.¹⁰ demonstrated that serum amylase levels were more than threefold elevated in only 7% of patients with CKD and serum lipase levels of >300 μg/L (>60 IU/L) are unusual in patients with renal failure and may be indicative of pancreatitis. Similarly, Masoero et al.¹¹ had demonstrated that serum amylase levels were more than threefold elevated in only 7% of patients with ESRD, and serum lipase levels were elevated in 3% of patients with CKD and 10% of patients with ESRD. Thus, the diagnosis of acute pancreatitis in patients with CKD is generally made when there is a clinically suspicion and an elevation of serum amylase and lipase levels more than 3 times above the upper limit of normal or if this level of elevation is absent, but there is an abnormal radiological investigation (USG or CT scan).³

A high incidence of morbidity and mortality has been reported in patients with CKD developing acute pancreatitis. CKD patients can develop acutely worsening renal function, with 28% of patients needing dialysis. Even though a recent study shows a low mortality rate of 2.3%, probably due to the high prevalence of pancreatitis of lesser severity,¹² the incidence in most studies is between 11% and 30% with the higher rates being in patients on PD.^8,11 This is similar to the mortality in the general population who have necrotizing pancreatitis (up to 30%), which is the more severe form of pancreatitis.^13,14

CONCLUSION

Acute pancreatitis is one of the causes of acute abdomen in CKD patients. In view of its high morbidity and mortality in this population, this differential diagnosis should always be considered. The exact pathogenetic mechanisms contributing to an increased incidence in patients on CAPD are not exactly known and warrant further studies.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.