Combination therapy with immune check point inhibitors and acute kidney injury.

BACKGROUND: Immune checkpoint inhibitors have revolutionized the treatment of metastatic renal cell carcinoma and malignant melanoma but are also associated with a risk of severe side effects. Nephrotoxicity is an immune checkpoint inhibitor-related adverse effect, but acute kidney injury (AKI) can also be caused by other more common conditions. This study aimed to describe the incidence and causes of AKI in patients treated with combination therapy of immune checkpoint inhibitors. MATERIAL AND METHODS: This retrospective cohort study included 200 patients receiving ipilimumab and nivolumab for either metastatic renal cell carcinoma or malignant melanoma at the Department of Oncology at Copenhagen University Hospital, Herlev between 1 January 2019 and 31 December 2020. The incidence and cause of AKI within 6 months after treatment was determined. RESULTS: In the 96 patients treated for malignant melanoma 15 patients (16%) had an episode of AKI. Two of these patients had potential immune checkpoint inhibitor-related AKI both of which received treatment with a proton pump inhibitor (PPI). Of the 104 included patients with metastatic renal cell carcinoma 26 patients (25%) developed AKI. Five of these patients had potential immune checkpoint inhibitor-related AKI. Treatment with PPI before the development of AKI occurred in 4 out of these 5 patients. CONCLUSION: Patients receiving combination therapy with checkpoint inhibitors are at high risk of AKI, but different causes of AKI should always be considered. Use of PPI concurrently with ICIs is likely to increase the risk of AKI.

Gastrointestinal motility in patients with end-stage renal disease on chronic hemodialysis.

BACKGROUND: Previous studies indicated delayed gastric emptying in patients with end-stage renal disease (ESRD) using indirect methods. The objective of the current study was to examine gastrointestinal motility using a direct method as well as the role of the incretin hormones and glucagon. METHODS: Patients on chronic hemodialysis and with either normal glucose tolerance, impaired glucose tolerance or type 2 diabetes, and healthy control subjects (N = 8, respectively) were studied. Gastric emptying time was measured by repeated gamma camera imaging for 6 hours after intake of a radioactive labeled standardized mixed solid and liquid meal. Glucagon, glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) levels were measured. KEY RESULTS: Patients were age, gender and BMI matched with controls. We found significantly higher gastric retention at 15 minutes, prolonged gastric mean emptying time, and gastric half-emptying time of the solid marker in all three groups of ESRD patients compared to controls. Significant differences in mean total area under the concentration curve (AUC) values across the four groups for GIP (P = 0.001), but not for GLP-1 and glucagon. The ESRD group had significant higher total AUC of GIP and glucagon compared to controls (P < 0.001 and P < 0.04) but not for GLP-1 (P = 0.4). No difference in incremental AUC was found. CONCLUSIONS AND INFERENCES: We found altered gastrointestinal motility in dialysis patients, with higher gastric retention and prolonged gastric emptying, and higher total AUC of GIP and glucagon independent of the presence of diabetes or prediabetes.

Treatment of a soft tissue calcification in a patient receiving peritoneal dialysis.

Chronic Kidney Disease patients suffer from Mineral and Bone Disorder (CKD-MBD) leading to increased vascular and soft-tissue calcification. The prevalence of soft tissue calcification in dialysis patients is not well described, and most cases describe such calcifications in hemodialysis patients. We describe a case of a massive soft tissue calcification in the right gluteal region in a peritoneal dialysis patient. The patient had severe pain and were disabled. The treatment was converted to an intensive hemodialysis regimen with a minimal calcium load and high dose of cinacalcet. During the treatment, the calcification diminished rapidly from a diameter of 26.6 to 2.9 cm, and the patient symptoms were relieved, leaving the patient with no pain or restriction in mobilization.

[Clinical use of estimated glomerular filtration rate for evaluation of kidney function]. / Klinisk anvendelse af estimeret glomerulær filtrationshastighed til vurdering af nyrefunktionen.

Estimating glomerular filtration rate by the Modification of Diet in Renal Disease or Chronic Kidney Disease Epidemiology Collaboration formulas gives a reasonable estimate of kidney function for e.g. classification of chronic kidney disease. Additionally the estimated glomerular filtration rate is a significant predictor for cardiovascular disease and may along with classical cardiovascular risk factors add useful information to risk estimation. Several cautions need to be taken into account, e.g. rapid changes in kidney function, dialysis, high age, obesity, underweight and diverging and unanticipated deviations in muscle mass may make the estimate unreliable.