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Since their introduction into clinical practice a decade ago, immune checkpoint inhibitors (ICIs) have had an overwhelming impact on cancer treatment. Use of these agents in oncology continues to grow; however, the increased use of these agents has been associated with a parallel increase in ICI-associated immune-related adverse events, which can affect virtually any organ, including the kidneys. ICI-associated acute kidney injury (ICI-AKI) occurs in 2-5% of patients treated with ICIs. Its occurrence can have important consequences, including the temporary or permanent discontinuation of ICIs or other concomitant anticancer therapies and the need for prolonged treatment with corticosteroids. Various mechanisms have been proposed to underlie the development of ICI-AKI, including loss of tolerance to self-antigens, reactivation of drug-specific effector T cells, and the production of kidney-specific autoantibodies. ICI-AKI most commonly manifests as acute tubulo-interstitial nephritis on kidney biopsy and generally shows a favourable response to early initiation of corticosteroids, with complete or partial remission achieved in most patients. The evaluation of patients with suspected ICI-AKI requires careful diagnostic work-up and kidney biopsy for patients with moderate-to-severe ICI-AKI to ensure accurate diagnosis and inform appropriate treatment.

Background Immune checkpoint inhibitors (ICPIs) are a novel therapeutic approach to cancer treatment that have changed the landscape of cancer therapy but also have some considerable drawbacks. Acute kidney injury (AKI) is one of these potential complications that may have effects on patient outcomes. In this review, we assessed the effect of AKI on mortality outcomes in cancer patients receiving this immunotherapy. Methods We performed a systematic review and meta-analysis of prospective, retrospective, randomized and non-randomized studies, which examined the effects of AKI in cancer patients receiving immune checkpoint inhibitors. We searched through PubMed, Medline, Web of Science, Scopus and Cochrane Library databases. Results Seven studies were included in the final analysis, with a total number of patients of 761. Overall, the risk of death was higher in patients that developed AKI during ICPI treatment [hazard ratio (HR) 1.42, 95% confidence interval (CI) 1.05–1.92, P = 0.02; heterogeneity χ2 = 11.68, I2 = 66%, P = 0.02] compared with patients that did not develop AKI. In addition, there was a trend to a better survival in those with less severe AKI patients compared with those with more severe AKI (HR 1.35, 95% CI 0.99–1.83, P = 0.05). Lastly, it was seen that patients with persistent kidney dysfunction (non-recovery) had an increased risk for all-cause mortality (HR 2.93, 95% CI 1.41–6.08, P = 0.004; heterogeneity χ2 = 0.53, I2 = 0%, P = 0.47). Conclusions Development of AKI in patients with cancer receiving immune checkpoint inhibitors is associated with increased risk of mortality.

Medications are a common cause of AKI, especially for patients admitted to hospital wards and the intensive care unit. Although drug-related kidney injury occurs through different mechanisms, this review will focus on three specific types of tubulointerstitial injury. Direct acute tubular injury develops from several medications, which are toxic to various cellular functions. Their excretory pathways through the proximal tubules contribute further to AKI. Drug-induced AKI may also develop through induction of inflammation within the tubulointerstitium. Medications can elicit a T cell-mediated immune response that promotes the development of acute interstitial nephritis leading to AKI. Although less common, a third pathway to kidney injury results from the insolubility of drugs in the urine leading to their precipitation as crystals within distal tubular lumens, causing a crystalline-related AKI. Intratubular obstruction, direct tubular injury, and localized inflammation lead to AKI. Clinicians should be familiar with the pathogenesis and clinical-pathologic manifestations of these forms of kidney injury. Prevention and treatment of AKI relies on understanding the pathogenesis and judiciously using these agents in settings where AKI risk is high.

Crystalline nephropathies are a unique form of kidney disease characterized by the histologic finding of intrarenal crystal deposition. The intrinsic nature of some molecules and ions combined with a favorable tubular fluid physiology leads to crystal precipitation and deposition within the tubular lumens. Crystal deposition promotes kidney injury through tubular obstruction and both direct and indirect cytotoxicities. Further kidney injury develops from inflammation triggered by these crystals. From a clinical standpoint, the crystalline nephropathies are associated with abnormal urinalysis and urinary sediment findings, tubulopathies, acute kidney injury (AKI), and/or chronic kidney disease (CKD). Urine sediment examination is often helpful in alerting clinicians to the possibility of crystal-related kidney injury. The identification of crystals within the kidneys on biopsy by pathologists prompts clinicians to evaluate patients for medication-related kidney injury, dysproteinemia-related malignancies, and certain inherited disorders. This review will focus on the clinical and pathologic aspects of these 3 categories of crystalline nephropathies.

Chemotherapeutic agents used to treat cancer generally have narrow therapeutic indices along with potentially serious adverse toxicities. Many cancer drugs are at least partially excreted through the kidney and, thus, the availability of accurate data on safe and effective dosing of these drugs in patients with chronic kidney disease (CKD) is essential to guide treatment decisions. Typically, during drug development, initial clinical studies only include patients with normal or only mildly impaired kidney function. In subsequent preregistration studies, a limited number of patients with more severe kidney dysfunction are included. Data obtained from patients with either severe kidney dysfunction (here defined as an estimated glomerular filtration rate [eGFR] < 30 ml/min or stage 4G CKD) or end-stage kidney disease (ESKD) requiring kidney replacement treatment are particularly limited before drug registration and only a minority of new drug applications to the US Food and Drug Administration (FDA) include data from this population. Unfortunately, limited data and/or other safety concerns may result in a manufacturer statement that the drug is contraindicated in patients with advanced kidney disease, which hinders access to potentially beneficial drugs for these patients. This systemic exclusion of patients with CKD from cancer drug trials remains an unsolved problem, which prevents provision of optimal clinical care for these patients, raises questions of inclusion, diversity, and equity. In addition, with the aging of the population, there are increasing numbers of patients with CKD and cancer who face these issues. In this review, we evaluate the scientific basis to exclude patients with CKD from cancer trials and propose a comprehensive strategy to address this problem. ispartof: KIDNEY INTERNATIONAL REPORTS vol:7 issue:9 pages:1939-1950 ispartof: location:United States status: published

Poly (ADP-ribose) polymerases (PARPs) are crucial in repairing DNA after a damaging event. However, several studies indicate that more extensive DNA disruption causes overactivity of PARP and can ultimately lead to cellular necrosis particularly in the setting of ischemia- related or sepsis-related acute kidney injury (AKI). Though the anti-cancer effects of PARP inhibitors (PARPis) are well known, especially in cases of Breast Cancer gene mutations, there exists a potential for the use of these drugs in treating ischemic AKI. Though the beneficial effects of PARPis in attenuating ischemic AKI has been shown in animal models, testing has yet to be done in humans. Studies have also found that PARPis interact with proximal tubular transporter channels and cause a physiologic increase serum creatinine, however the long- term effects on kidney function, proteinuria and hematuria are unclear. The use of PARPis in patients with chronic kidney disease (CKD) and malignancy may result in the amplification of adverse effects such as anemia and thrombocytopenia. Safe dosing of these agents in patients with advanced CKD and end stage kidney disease (ESKD) is yet to be determined as these populations were excluded from clinical trials. This manuscript reviews the current data on the kidney effects of PARPis and opens the door to further research in this arena.

Inaugural consensus statements were developed and endorsed by the American College of Radiology (ACR) and National Kidney Foundation to improve and standardize the care of patients with kidney disease who have indication(s) to receive ACR-designated group II or group III intravenous gadolinium-based contrast media (GBCM). The risk of nephrogenic systemic fibrosis (NSF) from group II GBCM in patients with advanced kidney disease is thought to be very low (zero events following 4931 administrations to patients with estimated glomerular filtration rate [eGFR]

Immunotherapy with immune checkpoint inhibitors (ICPi) may cause acute kidney injury (AKI) and their use is increasing.This is a single-center retrospective cohort study of patients receiving ICPi drugs for solid organ malignancies. ICPi-related AKI, the need for renal replacement therapy during or following ICPi treatment, and the associated mortality was studied.Two hundred thirty five patients were included in the final analysis. Patients with (N = 40) and without (n = 195) AKI had similar age, sex, type of ICPi, baseline serum creatinine levels, comorbidities and mortality; while patients with AKI were more likely to be receiving a nephrotoxic agent or be treated for genitourinary malignancy. 18 patients had ICPi-related AKI; 7 of these patients underwent kidney biopsy, which showed acute interstitial nephritis while the remaining 11 were diagnosed on clinical parameters. 18 (45%) patients recovered kidney function after AKI. No differences were observed between patients with and without kidney function recovery, although patients without recovery had a numerical, but not statistically significant, higher mortality. Patients with biopsy-confirmed ICPi-induced AKI had an increased risk of mortality, as compared with the rest of the population-HR 1.83, 95% CI 1.22-2.74, p = 0.003.Use of nephrotoxic drugs and the location of malignancy appear to be common drivers of AKI in patients receiving ICPis for solid organ malignancy. Whether nephrotoxic agents or urinary tract obstruction may favor ICPi-related autoimmunity should be further studied.

In discussing the educational value of clinical images used in medicine, it is worth briefly touching on some of the history behind the birth and evolution of medical illustrations (1). Illustration of various maladies have appeared in manuscripts from ancient times where religion, spirituality, and science where incorporated into these “medical illustrations.” In the early third century BC, medical illustration for the purpose of instruction appeared in Hellenic Alexandria. These medical illustrations demonstrated a variety of aspects of medicine including medicinal plants, anatomy, surgery, and obstetrics. Leonardo da Vinci, considered the first “contemporary” medical illustrator, combined artistic skill with a scientific understanding of anatomy to create medical illustrations. Andreas Vesalius followed and published one of the most well …

Case Answer A 58-year-old man with nephrotic syndrome (8 g of protein per 24 hours and serum albumin 1.6 g/dl) due to biopsy-proven idiopathic membranous nephropathy (Figure 1A) diagnosed 3 weeks prior developed acute onset of right flank pain. Serum creatinine was 1.9 mg/dl (baseline, 0.9 mg/dl). Urinalysis demonstrated 1+ blood and 3+ protein, whereas urine microscopy revealed 30 isomorphic red blood cells per high power field. A computed-tomography angiogram of the abdomen (Figure 1B) was undertaken and it revealed an extensive right renal vein thrombus (RVT) (yellow arrow) extending into the inferior vena cava (white arrow) on venous phase imaging. The patient underwent percutaneous catheter thrombectomy and local thrombolytic therapy with recombinant tissue plasminogen activator followed by a heparin drip, which was transitioned to warfarin. …

Background We previously demonstrated that urine interleukin (IL)-9 and tumor necrosis factor (TNF)-α can distinguish acute interstitial nephritis (AIN) from other causes of acute kidney injury. Here we evaluated the role of these biomarkers to prognosticate kidney function in patients with AIN. Methods In a cohort of participants with biopsy-proven, adjudicated AIN, we tested the association of histological features and urine biomarkers (IL-9 and TNF-α) with estimated glomerular filtration rate measured 6 months after diagnosis (6 m-eGFR) controlling for eGFR before AIN and albuminuria. We also evaluated subgroups in whom corticosteroid use was associated with 6 m-eGFR. Results In the 51 (93%) of the 55 participants with complete data, median (interquartile range) eGFR before and 6 m after AIN were 41 (27–69) and 28 (13–47) mL/min/1.73 m2, respectively. Patients with higher severity of interstitial fibrosis had lower 6 m-eGFR, whereas those with higher tubulointerstitial infiltrate had higher 6 m-eGFR. IL-9 levels were associated with lower 6 m-eGFR only in the subset of patients who did not receive corticosteroids [6m-eGFR per doubling of IL-9, −6.0 (−9.4 to −2.6) mL/min/1.73 m2]. Corticosteroid use was associated with higher 6 m-eGFR [20.9 (0.2, 41.6) mL/min/1.73 m2] only in those with urine IL-9 above the median (>0.66 ng/g) but not in others. Conclusions Urine IL-9 was associated with lower 6 m-eGFR only in participants not treated with corticosteroids. Corticosteroid use was associated with higher 6 m-eGFR in those with high urine IL-9. These findings provide a framework for IL-9-guided clinical trials to test efficacy of immunosuppressive therapy in patients with AIN.

The management of pain in patients with chronic kidney disease (CKD) is challenging for many reasons. These patients have increased susceptibility to adverse drug effects due to altered drug metabolism and excretion, and there are limited safety data for use in this population despite a high pain burden. Nonsteroidal anti-inflammatory drugs (NSAIDs) have long been regarded as dangerous for use in patients with CKD because of their risk for nephrotoxicity and thus alternative classes of analgesics, including opioids, have become more commonly used for pain control in this population. Given the well-established risks that opioids and other analgesics pose, further characterization of the risk posed by NSAIDs in patients with CKD is warranted. NSAID use has been associated with acute kidney injury, progressive loss of glomerular filtration rate in CKD, electrolyte derangements, and hypervolemia with worsening of heart failure and hypertension. The risk for these nephrotoxicity syndromes is modified by many comorbid conditions, risk factors, and characteristics of use, and in patients with CKD, the risk differs between levels of glomerular filtration rate. In this review, we offer recommendations for the cautious use of NSAIDs in the CKD population after careful consideration of these risk factors on an individualized basis.

The worldwide burden of kidney disease is rising, but public awareness remains limited, underscoring the need for more effective communication by stakeholders in the kidney health community. Despite this need for clarity, the nomenclature for describing kidney function and disease lacks uniformity. In June 2019, Kidney Disease: Improving Global Outcomes (KDIGO) convened a Consensus Conference with the goal of standardizing and refining the nomenclature used in the English language to describe kidney function and disease, and of developing a glossary that could be used in scientific publications. Guiding principles of the conference were that the revised nomenclature should be patient-centered, precise, and consistent with nomenclature used in the KDIGO guidelines. Conference attendees reached general consensus on the following recommendations: (i) to use "kidney" rather than "renal" or "nephro-" when referring to kidney disease and kidney function; (ii) to use "kidney failure" with appropriate descriptions of presence or absence of symptoms, signs, and treatment, rather than "end-stage kidney disease"; (iii) to use the KDIGO definition and classification of acute kidney diseases and disorders (AKD) and acute kidney injury (AKI), rather than alternative descriptions, to define and classify severity of AKD and AKI; (iv) to use the KDIGO definition and classification of chronic kidney disease (CKD) rather than alternative descriptions to define and classify severity of CKD; and (v) to use specific kidney measures, such as albuminuria or decreased glomerular filtration rate (GFR), rather than "abnormal" or "reduced" kidney function to describe alterations in kidney structure and function. A proposed 5-part glossary contains specific items for which there was general agreement. Conference attendees acknowledged limitations of the recommendations and glossary, but they considered standardization of scientific nomenclature to be essential for improving communication.

Intravenous iodinated contrast media are commonly used with CT to evaluate disease and to determine treatment response. The risk of acute kidney injury (AKI) developing in patients with reduced kidney function following exposure to intravenous iodinated contrast media has been overstated. This is due primarily to historic lack of control groups sufficient to separate contrast-induced AKI (CI-AKI; ie, AKI caused by contrast media administration) from contrast-associated AKI (CA-AKI; ie, AKI coincident to contrast media administration). Although the true risk of CI-AKI remains uncertain for patients with severe kidney disease, prophylaxis with intravenous normal saline is indicated for patients who have AKI or an estimated glomerular filtration rate less than 30 mL/min/1.73 m2 who are not undergoing maintenance dialysis. In individual high-risk circumstances, prophylaxis may be considered in patients with an estimated glomerular filtration rate of 30–44 mL/min/1.73 m2 at the discretion of the ordering clinician.

BackgroundIn patients receiving immune checkpoint inhibitor (ICI) therapy, acute kidney injury (AKI) is common, and can occur either from kidney injury unrelated to ICI use or from immune activation resulting in acute interstitial nephritis (AIN). In this study, we test the hypothesis that occurrence of AIN indicates a favorable treatment response to ICI therapy and therefore among patients who develop AKI while on ICI therapy, those with AIN will demonstrate greater survival compared with others with AKI.MethodsIn this observational cohort study, we included participants initiated on ICI therapy between 2013 and 2019. We tested the independent association of AKI and estimated AIN (eAIN) with mortality up to 1 year after therapy initiation as compared with those without AKI using time-varying Cox proportional hazard models controlling for demographics, comorbidities, cancer type, stage, and therapy, and baseline laboratory values. We defined eAIN as those with a predicted probability of AIN >90th percentile derived from a recently validated diagnostic model.ResultsOf 2207 patients initiated on ICIs, 617 (28%) died at 1 year and 549 (25%) developed AKI. AKI was independently associated with higher mortality (adjusted HR, 2.28 (95% CI 1.90 to 2.72)). Those AKI patients with eAIN had more severe AKI as reflected by a higher peak serum creatinine (3.3 (IQR 2.1–6.1) vs 1.4 (1.2–1.9) mg/dL, pConclusionIn patients treated with ICI, mortality was higher in those with AKI unrelated to ICI but lower in those where the underlying etiology was AIN. Future studies could evaluate the association of biopsy-proven or biomarker-proven AIN with mortality in those receiving ICI therapy.

Background Patients with acute interstitial nephritis (AIN) can present without typical clinical features, leading to a delay in diagnosis and treatment. We therefore developed and validated a diagnostic model to identify patients at risk of AIN using variables from the electronic health record. Methods In patients who underwent a kidney biopsy at Yale University between 2013 and 2018, we tested the association of >150 variables with AIN, including demographics, comorbidities, vital signs and laboratory tests (training set 70%). We used least absolute shrinkage and selection operator methodology to select prebiopsy features associated with AIN. We performed area under the receiver operating characteristics curve (AUC) analysis with internal (held-out test set 30%) and external validation (Biopsy Biobank Cohort of Indiana). We tested the change in model performance after the addition of urine biomarkers in the Yale AIN study. Results We included 393 patients (AIN 22%) in the training set, 158 patients (AIN 27%) in the test set, 1118 patients (AIN 11%) in the validation set and 265 patients (AIN 11%) in the Yale AIN study. Variables in the selected model included serum creatinine {adjusted odds ratio [aOR] 2.31 [95% confidence interval (CI) 1.42–3.76]}, blood urea nitrogen:creatinine ratio [aOR 0.40 (95% CI 0.20–0.78)] and urine dipstick specific gravity [aOR 0.95 (95% CI 0.91–0.99)] and protein [aOR 0.39 (95% CI 0.23–0.68)]. This model showed an AUC of 0.73 (95% CI 0.64–0.81) in the test set, which was similar to the AUC in the external validation cohort [0.74 (95% CI 0.69–0.79)]. The AUC improved to 0.84 (95% CI 0.76–0.91) upon the addition of urine interleukin-9 and tumor necrosis factor-α. Conclusions We developed and validated a statistical model that showed a modest AUC for AIN diagnosis, which improved upon the addition of urine biomarkers. Future studies could evaluate this model and biomarkers to identify unrecognized cases of AIN.

The debate in this issue of Kidney360 addresses the quandary that exists regarding the safety of nonsteroidal anti-inflammatory drug (NSAID) use in patients with CKD. This is an important issue because pain syndromes are common in patients with CKD. Whereas NSAIDs are a widely used and effective analgesic, they can be associated with several adverse clinical kidney syndromes (Table 1), particularly in patients with underlying CKD (1,2). Clinicians struggle to achieve adequate analgesia while also avoiding toxicity in this group. However, is avoiding NSAIDs in patients with CKD too restrictive and unnecessary? Our two expert debaters Erin Baretto and Bruce Guthrie tackle the conundrum of whether NSAIDs can be safely used in patients with nondialysis CKD. They will present the PRO and CON sides of the debate. We provide background on NSAID therapy in patients with CKD to set the stage for the debate. View this table: Table 1. Clinical kidney syndromes of nonsteroidal anti-inflammatory drugs Pain management in patients with CKD is limited by a number of analgesic drug-related adverse effects (3). Reduced GFR and impaired tubular secretion put patients with AKI or CKD at increased risk of drug-related nephrotoxicity because of increased accumulation of parent drugs, and their metabolites, from impaired metabolism and excretion (4). A significant number of drugs with potential toxicity are concomitantly prescribed to patients with advanced CKD (5). As such, NSAIDs are considered a class of drugs that should be avoided in patients with CKD, particularly those with advanced CKD (6,7). This approach has led to increased opioid administration and …

Medications are a relatively common cause of acute kidney injury (AKI), especially in hospitalized patients who are exposed to numerous agents. Drug-related acute tubular/tubulointerstitial injury is the most common cause of AKI associated with these agents. Toxic effects of drugs and their renal handling often lead to various forms of AKI.The inherent nephrotoxicity of drugs and their transport and metabolism by the kidneys play an important role in the occurrence of acute tubular injury. Apical transport of the aminoglycosides by endocytosis and apical pinocytosis of filtered hydroxyethyl starch into cells lead to acute tubular dysfunction. Transport of tenofovir and cisplatin by organic anion and cation transporters in the basolateral surface of the proximal tubule, respectively, are associated with intracellular drug accumulation and injury. Intratubular deposition of drug crystals with associated AKI occurs with several drugs, in particular the anticancer agent methotrexate. A potentially new mechanism of drug-induced AKI was described with vancomycin - acute vancomycin-related cast nephropathy. Immune-mediated acute tubulointerstitial injury is another cause of drug-induced AKI, as seen with immune checkpoint inhibitors.Drugs lead to AKI through mechanisms that involve their inherent toxicity as well as their transport and handling by the kidneys.

Aims Acute and chronic kidney dysfunction is common in patients with end-stage liver disease. Differentiation between acute kidney injury (AKI) due to hepatorenal syndrome (HRS) or acute tubular necrosis (ATN) remains difficult, however urine cast scoring systems using renal tubular epithelial cells (RTECs) and granular casts (GCs) can help to identify intrinsic kidney diseases. The objective of this study was to evaluate the urine sediment profile of patients with liver disease and hyperbilirubinemia/hyperbilirubinuria and the use of a urine sediment scoring system to identify the most common score in AKI patients and high urine bilirubin concentrations. Materials and methods A retrospective study in the database of a large laboratory that assists a hospital-complex in Brazil was performed. Results Urinary casts, in particular GCs, as well as RTECs were observed more frequently in patients with hyperbilirubinemia/hyperbilirubinuria, while hyaline casts were observed in patients without hyperbilirubinemia/hyperbilirubinuria. Regardless of the AKI or non-AKI condition, the relative risk for scores 2 or 3 (sediment consistent with tubular damage, with GCs and/or RTECs in different quantities) in group 4 was 3.61 times higher compared to patients in group 1. Conclusion In patients with higher urinary bilirubin levels, the urine sediment had greater numbers of GCs and RTECs and higher urine sediment scores (scores 2 or 3). The presence of a larger number of urine particles (RTECs and GCs) originating in the kidneys in the groups with higher levels of urinary bilirubin suggests an association between hyperbilirubinemia/hyperbilirubinuria and tubular injury independent of AKI or non-AKI.

Introduction: Advanced cancers that did not respond to chemotherapy were once a death sentence, but now there are newer therapies utilizing the patient’s own immune system to fight cancer that are ...

Over the past decade, Onco-Nephrology has emerged as an important sub-field of not only nephrology and oncology but also hematology, urology, critical care medicine, clinical pharmacology, and palliative care medicine. This nexus reflects the unique connection that exists for kidney disease and cancer in all of clinical medicine. As noted, Onco-Nephrology combines the knowledge and skills of a number of specialty groups that span all areas of medicine. In this issue of the Journal of Onco-Nephrology, a series of papers addressing the various forms of kidney disease that develop in patients with cancer and its therapy is presented as part of the Onco-Nephrology Highlights section. These papers are based on the Onco-Nephrology Symposium that took place at MD Anderson Cancer Center in 2018. We hope you find these six papers educational and practical as you evaluate and treat patients with cancer and kidney disease in your clinical practice.

Automated urine technology and centralized laboratory testing are becoming the standard for providing urinalysis data to clinicians, including nephrologists. This trend has had the unintended consequence of making examination of urine sediment by nephrologists a relatively rare event. In addition, the nephrology community appears to have lost interest in and forgotten the utility of provider-performed urine microscopy. However, it is critical to remember that urine sediment examination remains a time-honored test that provides a wealth of information about the patient's underlying kidney disease. This test performs very favorably as a urinary "biomarker" for a number of acute kidney diseases. When used properly, urine sediment findings alert health care providers to the presence of kidney disease, while also providing diagnostic information that often identifies the compartment of kidney injury. Urine sediment findings may also guide therapy and assist in prognostication. In this review of the role of urine sediment examination in the diagnosis and management of kidney disease, we seek to help experienced nephrologists maintain their competency in performing this test and encourage ongoing training of nephrology fellows and others less experienced in such analyses.

Nephrotoxicity associated with immunotherapy is increasingly being encountered in clinical practice. Drugs that augment the immune system to eradicate cancer are revolutionary in the field of oncology. Older generation immunotherapies such as high-dose interleukin and interferon-alpha are now being replaced with more effective immune checkpoint inhibitors and chimeric antigen receptor T-cell therapies, which have shown promising results in numerous clinical trials. Unfortunately, these treatments come with a unique baggage of adverse effects including nephrotoxicity. This onconephrology review summarizes the immunotherapies currently in use and their kidney-related toxicities, pathophysiology, and their management.

Acute interstitial nephritis (AIN) is a well-known cause of acute kidney disease (AKD) and CKD and is associated with progression to ESKD (1⇓⇓⇓⇓–6). Accordingly, it represents an important problem for clinicians caring for these patients. AIN is primarily an immune-mediated kidney injury triggered by use of certain medications, in particular antibiotics, PPIs, NSAIDs, and immune checkpoint inhibitors (ICPIs), or by autoimmune diseases, such as Sjogren syndrome, sarcoidosis, IgG4-related tubulointerstitial disease, and TINU. In developed countries, medications are the most common cause of AIN (>70%), whereas the number approximates 50% in developing countries. Infectious agents are a less common cause of AIN, except in developing countries. The overall incidence of AIN in kidney biopsy registries is 2%–5%, whereas AIN is observed in approximately 15%–20% of patients with AKI or AKD who undergo kidney biopsy (1⇓–3). The actual number is likely higher as many patients with AKI/AKD do not undergo biopsy and are presumed to have acute tubular injury (ATI). Importantly, diagnosing AIN clinically is often quite challenging, making kidney biopsy a frequent requirement to definitively confirm the diagnosis and guide therapy (Figure 1). Furthermore, delayed or missed AIN diagnosis leads to ongoing inflammation with resulting interstitial fibrosis, tubular atrophy, and permanent kidney damage, which may be the explanation for CKD occurring in 40%–60% of patients after an episode of AIN (4,5). Approximately 2% of CKD is considered to be due to AIN, which is equivalent to 10 million prevalent worldwide cases. Furthermore, AIN is the primary cause of ESKD in 3%–4% of incident patients (6). It is one of the few potentially treatable causes of AKI if identified and treated early. In view of these data, three key challenges that limit the diagnosis and management of patients suspected of having …

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment since their introduction ∼15 years ago. However, these monoclonal antibodies are associated with immune-related adverse events that can also affect the kidney, resulting in acute kidney injury (AKI), which is most commonly due to acute tubulointerstitial nephritis (ATIN). Limited data are available on the true occurrence of ICI-associated AKI. Furthermore, evidence to guide the optimal management of ICI-associated AKI in clinical practice is lacking. In this issue, Oleas et al. report a single-center study of patients with nonhematologic malignancies who received ICI treatment during a 14-month period, experienced AKI and underwent a kidney biopsy at the Vall d'Hebron University Hospital. Importantly, they demonstrate that only a minority of ICI-associated AKI patients was referred to the nephrology service and kidney biopsy was only performed in 6.4% of patients. Although the authors add to our knowledge about ICI-associated AKI, their article also highlights the need for the development of noninvasive diagnostic markers for ICI-associated ATIN, the establishment of treatment protocols for ICI-associated ATIN and recommendations for optimal ICI rechallenge in patients with previous ICI-associated AKI. ispartof: CLINICAL KIDNEY JOURNAL vol:14 issue:5 pages:1301-1306 ispartof: location:England status: published

Onco-nephrology is an emerging field in medicine. Patients with cancer may suffer from kidney diseases because of the cancer itself and cancer-related therapy. It is critical for nephrologists to be knowledgeable of cancer biology and therapy in order to be fully integrated in the multidisciplinary team and optimally manage patients with cancer and kidney diseases. In a recent international meeting, the key issues in this challenging clinical interface were addressed, including many unresolved basic science questions, such as the high tumor incidence in kidney transplant recipients. To this end, 70 highly qualified faculty members were gathered from all over the world to discuss these issues in 8 plenary sessions, including 5 keynote lectures. In addition, 48 young nephrologists and oncologists were invited to present their original observations that were highlighted in 2 large poster sessions.

Key Points Question What is the interobserver reliability among practicing nephrologists when interpreting urine sediment findings? Findings In this diagnostic study, 14 nephrologists provided 1064 interpretations of images of urine sediment findings. Agreement could be classified as slight, fair, moderate, substantial, or almost perfect. The interobserver reliability of urine sediment findings is mostly moderate to substantial but varies widely. Meaning Results of this study suggest that efforts to decrease variability in urine sediment interpretations may help increase the yield of this widely used test in medicine., Importance Urine sediment microscopy is commonly performed during the evaluation of kidney disease. Interobserver reliability of nephrologists’ urine sediment examination has not been well studied. Objective Assess interobserver reliability of the urine sediment examination. Design, Setting, and Participants In this diagnostic test study, urine samples were prospectively collected from a convenience sample of adult patients from an academic hospital in the United States undergoing kidney biopsy from July 11, 2018, to March 20, 2019. Digital images and videos of urine sediment findings were captured using a bright-field microscope. These images and videos along with urine dipstick results were incorporated in online surveys and sent to expert nephrologists at 15 US teaching hospitals. They were asked to identify individual sediment findings and the most likely underlying disease process. Exposures Urine dipstick results and urine sediment images from patients undergoing native kidney biopsy. Main Outcomes and Measures Interobserver reliability of urine sediment microscopy findings estimated by overall percent agreement and Fleiss κ coefficients. Secondary outcomes included concordance of diagnoses suspected by nephrologists with corresponding kidney biopsy results. Results In total, 10 surveys from 10 patients containing 76 study questions on individual features were sent to 21 nephrologists, 14 (67%) of whom completed them all. Their combined 1064 responses were analyzed. Overall percent agreement for casts was an estimated 59% (95% CI, 50%-69%), κ = 0.52 (95% CI, 0.42-0.62). For other sediment findings, overall percent agreement was an estimated 69% (95% CI, 61%-77%), κ = 0.65 (95% CI, 0.56-0.73). The κ estimates ranged from 0.13 (95% CI, 0.10-0.17) for mixed cellular casts to 0.90 (95% CI, 0.87-0.94) for squamous epithelial cells. Conclusions and Relevance In this study, substantial variability occurred in the interpretation of urine sediment findings, even among expert nephrologists. Educational or technological innovations may help improve the urine sediment as a diagnostic tool., This diagnostic study assesses interobserver reliability of nephrologist examination of urine sediment using high-resolution digital images and videos of the urine sediment of patients across the US undergoing kidney biopsy.