Renal alterations in cats (Felis catus) housed in shelters and affected by systemic AA-amyloidosis: Clinicopathological data, histopathology, and ultrastructural features.

AA-amyloidosis is frequent in shelter cats, and chronic kidney disease is the foremost cause of death. The aims were to describe kidney laboratory and microscopic findings in shelter cats with AA-amyloidosis. Cats were included if kidney specimens were collected post-mortem and laboratory data were available within 6 months before death. Renal lesions were evaluated with optical and electron microscopy. Mass spectrometry was used to characterize amyloid. Nine domestic short-hair cats were included; 4 females and 5 males with a median age of 8 years (range = 2-13). All cats had blood analyses and urinalyses available. Serum creatinine concentrations were increased in 6 cats and symmetric dimethylarginine was increased in all of the cats. All of the cats had proteinuria. Eight of 9 cats had amyloid in the medulla, and 9 had amyloid in the cortex (glomeruli). All cats had amyloid in the interstitium. Six cats had concurrent interstitial nephritis and 1 had membranoproliferative glomerulonephritis. All cats had extrarenal amyloid deposits. Amyloid was AA in each case. In conclusion, renal deposition of amyloid occurs in both cortex and medulla in shelter cats and is associated with azotemia and proteinuria. Renal involvement of systemic AA-amyloidosis should be considered in shelter cats with chronic kidney disease. The cat represents a natural model of renal AA-amyloidosis.

IL-6 mediates the hepatic acute phase response after prerenal azotemia in a clinically defined murine model.

Prerenal azotemia (PRA) is a major cause of acute kidney injury and uncommonly studied in preclinical models. We sought to develop and characterize a novel model of PRA that meets the clinical definition: acute loss of glomerular filtration rate (GFR) that returns to baseline with resuscitation. Adult male C57BL/6J wild-type (WT) and IL-6-/- mice were studied. Intraperitoneal furosemide (4 mg) or vehicle was administered at time = 0 and 3 h to induce PRA from volume loss. Resuscitation began at 6 h with 1 mL intraperitoneal saline for four times for 36 h. Six hours after furosemide administration, measured glomerular filtration rate was 25% of baseline and returned to baseline after saline resuscitation at 48 h. After 6 h of PRA, plasma interleukin (IL)-6 was significantly increased, kidney and liver histology were normal, kidney and liver lactate were normal, and kidney injury molecule-1 immunofluorescence was negative. There were 327 differentially regulated genes upregulated in the liver, and the acute phase response was the most significantly upregulated pathway; 84 of the upregulated genes (25%) were suppressed in IL-6-/- mice, and the acute phase response was the most significantly suppressed pathway. Significantly upregulated genes and their proteins were also investigated and included serum amyloid A2, serum amyloid A1, lipocalin 2, chemokine (C-X-C motif) ligand 1, and haptoglobin; hepatic gene expression and plasma protein levels were all increased in wild-type PRA and were all reduced in IL-6-/- PRA. This work demonstrates previously unknown systemic effects of PRA that includes IL-6-mediated upregulation of the hepatic acute phase response.NEW & NOTEWORTHY Prerenal azotemia (PRA) accounts for a third of acute kidney injury (AKI) cases yet is rarely studied in preclinical models. We developed a clinically defined murine model of prerenal azotemia characterized by a 75% decrease in measured glomerular filtration rate (GFR), return of measured glomerular filtration rate to baseline with resuscitation, and absent tubular injury. Numerous systemic effects were observed, such as increased plasma interleukin-6 (IL-6) and upregulation of the hepatic acute phase response.

Clinical significance of hypouricemia in children and adolescents.

BACKGROUND: Although hyperuricemia is a widely studied condition with well-known effects on the kidneys, hypouricemia is usually considered a biochemical abnormality of no clinical significance despite the fact that it can be a sign or major finding of serious metabolic or genetic diseases affecting kidney health. In this study, we aimed to investigate and emphasize the clinical significance of hypouricemia. METHODS: Patients were evaluated retrospectively for persistent hypouricemia defined as serum uric acid concentrations of < 2 mg/dL on at least 3 different occasions. According to the blood and urine uric acid (UA) levels, the patients were classified as having hypouricemia due to UA underproduction vs. overexcretion. Demographic, clinical, and genetic characteristics were noted for analysis. RESULTS: Fourteen patients (n = 14; M/F 8/6) with persistent hypouricemia were identified. Hypouricemia due to underproduction was the cause of 42.8% of these cases. All of the patients with a uric acid level of 0 mg/dL (n = 4) had hypouricemia due to underproduction. The median serum uric acid level was 0.85 (0-1.6) mg/dL. Isolated hypouricemia and hypouricemia with metabolic acidosis were equally distributed. Among the patients with hypouricemia due to underproduction, the final diagnoses were xanthine dehydrogenase deficiency (n = 5) and alkaptonuria (n = 1). In the overexcretion group, the final diagnoses were nephropathic cystinosis (n = 6), distal renal tubular acidosis (n = 1), and hereditary renal hypouricemia (n = 1). The diagnostic lag was longer for patients with isolated hypouricemia compared to other patients (p = 0.001). CONCLUSIONS: Hypouricemia may reflect underlying genetic or metabolic diseases, early diagnosis of which could help preserve kidney function. A higher resolution version of the Graphical abstract is available as Supplementary information.

Thrombotic microangiopathies after kidney transplantation in modern era: nosology based on chronology.

BACKGROUND: Thrombotic microangiopathies (TMAs) are rare but can be severe in kidney transplant. recipients (KTR). METHODS: We analysed the epidemiology of adjudicated TMA in consecutive KTR during the. 2009-2021 period. RESULTS: TMA was found in 77/1644 (4.7%) KTR. Early TMA (n = 24/77 (31.2%); 1.5% of all KTR) occurred during the first two weeks ((median, IQR) 3 [1-8] days). Triggers included acute antibody-mediated rejection (ABMR, n = 4) and bacterial infections (n = 6). Graft survival (GS) was 100% and recurrence rate (RR) was 8%. Unexpected TMA (n = 31/77 (40.2%); 1.5/1000 patient-years) occurred anytime during follow-up (3.0 (0.5-6.2) years). Triggers included infections (EBV/CMV: n = 10; bacterial: n = 6) and chronic active ABMR (n = 5). GS was 81% and RR was 16%. Graft-failure associated TMA (n = 22/77 (28.6%); 2.2% of graft losses) occurred after 8.8 (4.9-15.5) years). Triggers included acute (n = 4) or chronic active (n = 14) ABMR, infections (viral: n = 6; bacterial: n = 5) and cancer (n = 6). 15 patients underwent transplantectomy. RR was 27%. Atypical (n = 6) and typical (n = 2) haemolytic and uremic syndrome, and isolated CNI toxicity (n = 4) were rare. Two-third of biopsies presented TMA features. CONCLUSIONS: TMA are mostly due to ABMR and infections; causes of TMA are frequently combined. Management often is heterogenous. Our nosology based on TMA timing identifies situations with distinct incidence, causes and prognosis.

The impact of preoperative kidney replacement therapy on kidney outcome and survival in patients with left ventricular assist device.

Left ventricular assist device (LVAD) has been highlighted as a new treatment option in the end-stage heart failure (HF). Kidney outcome after LVAD in severe cardiorenal syndrome (CRS) patients requiring kidney replacement therapy (KRT) is unclear. We investigated the impact of preoperative KRT on kidney function and survival in LVAD patients with severe CRS. A total of 50 patients followed up for at least 1 year after LVAD implantation was analyzed. The primary outcomes were estimated glomerular filtration rate and survival rate. Patients were divided into two groups depending on in-hospital KRT before LVAD implantation: the control group (n = 33) and the KRT group (n = 17). Postoperative KRT was performed for 76.5% of patients in the KRT group, and all of them discontinued KRT before discharge. There were no statistically significant differences in the degree of eGFR decline in survivors according to preoperative KRT. Although there were no statistically significant differences in the degree of eGFR decline in survivors regardless of preoperative KRT, old age (ß -0.94, p < 0.01), preexisting chronic kidney disease (ß -21.89, p < 0.01), and high serum creatinine (ß -13.95, p < 0.01) were identified as independent predictors of post-LVAD eGFR decline. Mortality rate was higher, and more patients progressed to end-stage kidney disease in KRT group than control group. However, LVAD still can be considered as the treatment option in end-stage HF patients with severe CRS requiring KRT, especially in those with young age and previous normal kidney function.

RENAL PATHOLOGY IN CAPTIVE ADULT ALAOTRAN GENTLE LEMURS (HAPALEMUR ALAOTRENSIS).

Full medical histories from captive Alaotran gentle lemurs or Bandro (Hapalemur alaotrensis) > 1 yr old that died between 1990 and 2016 were requested from holding institutions. Eighty-six individuals died during the period analyzed. Full postmortem reports were received from 40 (46.5%) animals from 16 different institutions across Europe (15) and North America (1). Eighteen animals (45%) showed azotemia within three months of death, with accompanying histological renal lesions. Another 17 (42.5%) showed histological renal lesions, but no renal function assessment was carried out antemortem, or results were within normal limits. Only five animals (12.5%) showed no renal lesions. Of the 35 (87.5%) animals with histological renal lesions, 18 were females, and 17 were males, 11 were wild caught, and 24 were captive born. Twenty-seven animals were euthanized, seven were found dead, and in one case, no details were provided. Sixty-four blood samples from 22 animals were available. Azotemia was observed on average 407 d antemortem, with a case observed as early as 2,318 d antemortem. Twenty-nine urinalyses from 12 animals were carried out antemortem. All animals showed hematuria or proteinuria in at least one antemortem sample. A pH decrease from 8.5 to 5.0 was observed in two animals antemortem. Gross renal lesions most frequently reported were irregular surface (n = 14), abnormal shape (n = 12), and/or presence of cysts (n = 9). The most common histological lesions were interstitial nephritis (n = 25), interstitial fibrosis (n = 26), tubule dilation (n = 16), and glomerulosclerosis (n = 12). Development of additional diagnostic tools, standardization of ante- and postmortem diagnostic protocols, and further investigation into potential etiologies, such as diets offered in captivity and genetic factors, should be considered as the next steps for the veterinary management of this species in captivity.

Permissive azotemia during acute kidney injury enables more rapid renal recovery and less renal fibrosis: a hypothesis and clinical development plan.

Preclinical models of acute kidney injury (AKI) consistently demonstrate that a uremic milieu enhances renal recovery and decreases kidney fibrosis. Similarly, significant decreases in monocyte/macrophage infiltration, complement levels, and other markers of inflammation in the injured kidney are observed across multiple studies and species. In essence, decreased renal clearance has the surprising and counterintuitive effect of being an effective treatment for AKI. In this Perspective, the author suggests a hypothesis describing why the uremic milieu is kidney protective and proposes a clinical trial of 'permissive azotemia' to improve renal recovery and long-term renal outcomes in critically ill patients with severe AKI.

Changes in renal parameters and their association with subclinical vector-borne infections in Bernese Mountain dogs.

BACKGROUND: An increased risk for glomerulonephritis and a higher prevalence of antibodies to Borrelia (B.) burgdorferi sensu lato have been reported in Bernese mountain dogs (BMDs). The aim of the study was to determine the prevalence of laboratory abnormalities suggestive of kidney disease in clinically healthy BMDs compared to a control population and to investigate if there is a correlation with the occurrence of antibodies to B. burgdorferi sensu lato, Ehrlichia canis, and Anaplasma (A.) spp. and with the occurrence of Dirofilaria (D.) immitis antigen. A total of 197 BMDs and 57 control dogs were included in the study. Laboratory evidence of kidney disease was defined as renal azotemia and/or proteinuria with a urine protein creatinine ration of more than 0.5 in an inactive urine sediment. A SNAP®4Dx® ELISA (IDEXX, Laboratories, Inc., Westbrook, ME, USA) was used to detect antibodies to B. burgdorferi sensu lato, E. canis and Anaplasma spp. and antigen of D. immitis. RESULTS: Laboratory evidence of kidney disease was significantly more common in BMDs than in control dogs (17.8% versus 1.8%) (p = 0.005). The proportion of BMDs with anti-B. burgdorferi sensu latu antibodies and anti-A. phagocytophilum antibodies was significantly higher in BMDs (p <  0.001). However, an association between these findings could not be identified. CONCLUSION: BMDs are more often affected by kidney disease and have a higher prevalence of antibodies to bacterial pathogens transmitted by Ixodes ticks than control dogs. However, a causal relationship between these two variables could not be established due to a lack of association between these two findings.

Clinicopathological characteristics of light chain proximal tubulopathy in Korean patients and the diagnostic usefulness of immunohistochemical staining for immunoglobulin light chain.

BACKGROUND: Light chain proximal tubulopathy (LCPT) is a rare paraproteinemic renal disease that has been mostly reported in Western patients. LCPT is characterized by the accumulation of immunoglobulin (Ig)-light chain (LC) in the proximal tubule. Immunohistochemical staining for Ig-LC has not been investigated in the context of LCPT. We reported the clinicopathological characteristics and Ig-LC immunoexpression of patients with LCPT for the first time in Korea. METHODS: We reviewed the clinicopathological findings of 5 Korean patients diagnosed with LCPT between 2016 and 2018. In addition, immunohistochemical staining for κ-LC and λ-LC was conducted on paraffin-embedded tissues. RESULTS: The median age was 63 years, and the male-to-female ratio was 3:2. The primary renal manifestations were either azotemia or tubular proteinuria. All patients were diagnosed with multiple myeloma with monoclonal κ-LC (#1-2) or λ-LC (#3-5) in the serum and urine. Kidney biopsies revealed diverse and subtle alterations of the proximal tubule, including crystallization, vacuolization, and/or swelling. Electron microscopy revealed crystals in patients #1-2 and non-crystalline particles within numerous/large/dysmorphic lysosomes in patients #3-5. Ig-LC restriction was demonstrated in the proximal tubule as κ-type in patients #1-2 and as λ-type in patients #3-5 by immunohistochemistry and immunofluorescence. Immunohistochemical staining showed diffuse positivity to κ- and λ-LC, although immunofluorescent staining for κ-LC was focal and weak. LCPT has diverse clinicopathological characteristics and subtle morphological alterations, which necessitate ancillary tests for diagnosis. CONCLUSIONS: We introduced immunohistochemical staining for Ig-LC as a useful tool for the diagnosis of LCPT, especially in the case of κ-type crystals.

Non-diabetic glycosuria as a diagnostic clue for acute tubulointerstitial nephritis in patients with azotemia.

BACKGROUND: Glycosuria is one of the manifestations of acute tubulointerstitial nephritis (ATIN), but may also be observed in other renal diseases. In this study, we investigated the value of non-diabetic glycosuria as a diagnostic clue for ATIN. METHODS: We retrospectively reviewed the medical records of adult patients who underwent a kidney biopsy as an evaluation for serum creatinine > 1.4 mg/dL. Patients with proteinuria in the nephrotic range, diabetes mellitus, or transplanted kidney were excluded. The laboratory abnormalities suggestive of tubular injury were compared between 28 patients (14 men and 14 women, mean age 48.5 ± 14.1 years) with ATIN and 116 patients (76 men and 40 women, mean age 53.1 ± 15.0 years) with other diagnoses. RESULTS: In ATIN, glycosuria (≥ 1+ on dipstick; 68%) was more frequent than hypophosphatemia (18%), hypouricemia (18%), hypokalemia (18%), and tubular proteinuria (40%). In other diagnoses, glycosuria (≥ 1+) was detected in 7 (6%) patients; 6 of them had the histological diagnosis of antineutrophil cytoplasmic antibody-associated glomerulonephritis. The presence of glycosuria (≥ 1+) had 68% sensitivity and 94% specificity for ATIN, with the positive likelihood ratio of 11.24 and the negative likelihood ratio of 0.34. Pyuria and low total CO2 were equally and more sensitive (68% and 71%, respectively) than glycosuria (≥ 1+), but had no diagnostic value due to low specificities (58% and 60%, respectively). CONCLUSION: In non-diabetic, non-nephrotic patients undergoing a kidney biopsy for azotemia, 1+ or higher glycosuria, if present, was a good predictor of the diagnosis of ATIN.

Assessment and prediction of acute kidney injury in patients with decompensated cirrhosis with serum cystatin C and urine N-acetyl-ß-D-glucosaminidase.

BACKGROUND AND AIM: For appropriate management of acute kidney injury (AKI) in cirrhotic patients, accurate differentiation of the types of AKI, prerenal azotemia (PRA), hepatorenal syndrome (HRS), and acute tubular necrosis (ATN) is very important. Urine N-acetyl-ß-D-glucosaminidase (NAG) has been proposed as a good tubular injury marker in many studies, but its efficacy in cirrhosis is unclear. This study was performed to evaluate the usefulness of urine NAG in patients with decompensated cirrhosis. METHODS: In 114 hospitalized patients with decompensated cirrhosis, we assessed serum creatinine, cystatin C, and urine NAG levels as markers for AKI differentiation and development and patient mortality. RESULTS: Thirty patients diagnosed with AKI at baseline had significantly higher serum creatinine and cystatin C levels, urine NAG levels, and Child-Pugh scores than those without AKI. Only urine NAG levels were significantly higher in patients with ATN than those with PRA or HRS (116.1 ± 46.8 U/g vs 39.4 ± 20.2 or 54.0 ± 19.2 U/g urinary creatinine, all P < 0.05). During a median follow up of 6.1 months, AKI developed in 17 of 84 patients: PRA in nine, HRS in six, and ATN in three. Higher serum cystatin C and urine NAG levels were independent predictors of AKI development in patients with decompensated cirrhosis. Survival was significantly associated with low serum cystatin C and urine NAG levels. CONCLUSION: Serum cystatin C and urine NAG levels are useful to differentiate types of AKI and are strong predictors for AKI development and mortality in patients with decompensated cirrhosis.

GRHL2 Is Required for Collecting Duct Epithelial Barrier Function and Renal Osmoregulation.

Collecting ducts make up the distal-most tubular segments of the kidney, extending from the cortex, where they connect to the nephron proper, into the medulla, where they release urine into the renal pelvis. During water deprivation, body water preservation is ensured by the selective transepithelial reabsorption of water into the hypertonic medullary interstitium mediated by collecting ducts. The collecting duct epithelium forms tight junctions composed of barrier-enforcing claudins and exhibits a higher transepithelial resistance than other segments of the renal tubule exhibit. However, the functional relevance of this strong collecting duct epithelial barrier is unresolved. Here, we report that collecting duct-specific deletion of an epithelial transcription factor, grainyhead-like 2 (GRHL2), in mice led to reduced expression of tight junction-associated barrier components, reduced collecting duct transepithelial resistance, and defective renal medullary accumulation of sodium and other osmolytes. In vitro, Grhl2-deficient collecting duct cells displayed increased paracellular flux of sodium, chloride, and urea. Consistent with these effects, Grhl2-deficient mice had diabetes insipidus, produced dilute urine, and failed to adequately concentrate their urine after water restriction, resulting in susceptibility to prerenal azotemia. These data indicate a direct functional link between collecting duct epithelial barrier characteristics, which appear to prevent leakage of interstitial osmolytes into urine, and body water homeostasis.

Perspective on Clinical Application of Biomarkers in AKI.

Several biomarkers of renal injury have been identified but the utility of these biomarkers is largely confined to research studies, whereas widespread clinical applicability is limited. This is partly because the use of serum creatinine as the comparator has several limitations and restricts the full interpretation of biomarker performance. To highlight the potential for clinical application of biomarkers, the most pertinent biomarker data are summarized here, using clinically relevant scenarios in which biomarkers could assist with diagnostic and management dilemmas. The paradigms proposed in this review aim to enhance the clinical diagnosis, management, and prognosis of AKI through the combined use of available clinical markers and novel inflammatory, injury, and repair biomarkers.

Computed Tomographic Angiography of the Abdomen and Pelvis in Azotemic Patients Utilizing 80-kV(p) Technique and Reduced Dose Iodinated Contrast: Comparison With Routine 120-kV(p) Technique.

OBJECTIVE: To evaluate image quality (IQ) of a reduced contrast volume, low kilovolt (peak) [kV(p)] abdominopelvic computed tomographic angiography (AP-CTA) protocol compared to a standard 120-kV(p) AP-CTA protocol. METHODS: A retrospective image analysis was performed on 103 patients with end-stage renal disease who underwent AP-CTA. Forty-nine patients were scanned at 80 kV(p) with a mean of 48 mL of contrast, and 54 patients were scanned at 120 kV(p) with a mean of 98 mL of contrast. Objective comparison of arterial attenuation, noise, and contrast-to-noise ratio was obtained, in addition to radiation dose. Subjective assessment of IQ, enhancement intensity, and image noise (IN) was scored on a 3-point scale. RESULTS: The 6-level aggregate contrast-to-noise ratio for the 80-kV(p) group was 11.8 ± 7.0, compared to 12.4 ± 4.6 in the 120-kV(p) group (P = 0.210). Radiation exposure was significantly lower in the 80-kV(p) group versus the 120-kV(p) group, as measured by average CT dose index (mGy) of 9.0 ± 3.1 and 15.8 ± 5.8 (P < 0.0001), respectively; and average dose length product (mGy × cm) of 490.0 ± 214.1 and 863.1 ± 344.4 (P < 0.0001), respectively. The 120-kV(p) technique scored better for subjective IQ (P = 0.042) and IN (P = 0.004) but not for enhancement intensity (P = 0.205). CONCLUSIONS: A 50% reduced iodinated contrast dose coupled with 80-kV(p) technique with iterative reconstruction allows for satisfactory AP-CTA studies at a 43% mean radiation dose reduction compared to a standard protocol. Negative but potentially reversible sequelae of this drop in radiation dose include increased IN and reduced subjective IQ.

Significant decrease of saturation index in erythrocytes membrane from subjects with non-alcoholic fatty liver disease (NAFLD).

BACKGROUND: The lipidomic profiling of erythrocyte membranes is expected to provide a peculiar scenario at molecular level of metabolic and nutritional pathways which may influence the lipid balance and the adaptation and homeostasis of the organism. Considering that lipid accumulation in the cell is important in promoting tissue inflammation, the purpose of this study is to analyze the fatty acid profile in red blood cell membranes of patients with Non-Alcoholic Fatty Liver Disease (NAFLD), in order to identify and validate membrane profiles possibly associated with the degree of hepatic damage. METHODS: This work presents data obtained at baseline from 101 subjects that participated to a nutritional trial (registration number: NCT02347696) enrolling consecutive subjects with NAFLD. Diagnosis of liver steatosis was performed by using vibration-controlled elastography implemented on FibroScan. Fatty acids, extracted from phospholipids of erythrocyte membranes, were quantified by gas chromatography method. RESULTS: The subjects with severe NAFLD showed a significant decrease of the ratio of stearic acid to oleic acid (saturation index, SI) compared to controls, 1.281 ± 0.31 vs 1.5 ± 0.29, respectively. Low levels of SI in red blood cell membranes, inversely associated with degree of liver damage, suggest that an impairment of circulating cell membrane structure can reflect modifications that take place in the liver. Subjects with severe NAFLDalso showed higher levels of elongase 5 enzymatic activity, evaluated as vaccenic acid to palmitoleic acid ratio. CONCLUSIONS: Starting from these evidences, our findings show the importance of lipidomic approach in the diagnosis and the staging of NAFLD.

Fatal proteinuric kidney disease in a 30-month-old German Fleckvieh heifer caused by unilateral focal segmental glomerulosclerosis subsequent to a non-functional counterpart kidney.

INTRODUCTION: A case of secondary focal segmental glomerulosclerosis (FSGS) in a heifer is presented. A 30-month-old female German Fleckvieh heifer showed deterioration of the general condition, a poor nutritional status, proteinuria, hypoalbuminemia, and renal azotemia. Pathologically, it was diagnosed with unilateral hydronephrosis, and contralateral renal fibrosis with numerous cysts. Histologically, the fibrotic kidney showed FSGS, hyaline reabsorption droplets in proximal tubular epithelial cells, interstitial fibrosis, and tubulointerstitial inflammation. Apart from that, thrombotic microangiopathy (TMA) was seen in few renal arteries and meningeal arterioles. Pathogenesis of FSGS secondary to unilateral renal parenchymal loss (hydronephrosis) and TMA is discussed.

Nephroprotective Effect of EDL Peptide at Acute Injury of Kidneys of Different Genesis.

EDL peptide produced a nephroprotective effect on experimental models gentamycin-induced nephropathy and ischemia/reperfusion kidney injury in rats. The nephroprotective effect of EDL peptide manifested in prevention of oliguria and retention azotemia, a decrease in proteinuria and sodium excretion, prevention of critical decrease in activities of antioxidant enzymes, suppression of LPO, and normalization of energy supply to kidneys cells. Our findings confirm the prospects of further studies of the nephroprotective properties of peptide EDL in various pathologies of the kidneys.

Bone lymphoma with multiple negative bone biopsies.

This article describes a 71-year-old man with right knee pain, prerenal azotemia, hypercalcemia, and a mass in the distal femur. Although testing, including bone marrow biopsy, initially ruled out myeloma, an open surgical biopsy eventually confirmed the diagnosis as lymphoma involving the bone with classic histologic findings of mature B-cell neoplasm of germinal cell origin.