Dimensions of muddy brown granular casts in patients with acute tubular injury.

BACKGROUND: The presence of "muddy" brown granular casts (MBGC) in the urine sediment is pathognomonic for acute tubular injury (ATI). Although MBGC have been noted for years, there are no reports regarding their length nor width. The objective of this study was to measure MBGC using images obtained by light microscopy and investigate associations with clinically relevant parameters. METHODS: Patients with diagnosis of ATI as evidenced by visualization of abundant MBGC (>30% low power fields) were sampled. Bright-field images were measured using ImageJ. Twenty-five patients were included: 44% women; median age 64 yrs; 52% white, 36% black. Mean MBGC width (n = 350) was 34.4 ± 13.1 µm (range: 9 to 110 µm). RESULTS: Mean MBGC length was 98.7 ± 42.7 µm (range: 33 to 317 µm). Based on a previous report of cortical tubular diameters, MBGC width corresponded well with the median reported range. MBGC width was positively correlated with patient height (ρ=0.41, p=0.04), and length was positively correlated with fractional excretion of sodium (ρ=0.57. p=0.02) and urine chloride concentration (ρ=0.90, p=0.001). Mean MBGC length was negatively correlated with age (ρ=-0.47, p=0.02) and urine phosphate concentration (ρ=-0.72, p=0.03). There were no differences between cases that required renal replacement therapy (RRT, n =10) and those that did not require RRT (n=15). CONCLUSION: This is the first study reporting dimensions of MBGC from cases with ATI. Clinical implications of these observations require further study.

Concomitant Identification of Muddy Brown Granular Casts and Low Fractional Excretion of Urinary Sodium in AKI.

Background: Fractional excretion of urinary sodium (FENa) is a widely utilized clinical test to evaluate acute kidney injury (AKI). A low FENa (<1%) is deemed consistent with prerenal azotemia and inconsistent with acute tubular injury (ATI). Muddy brown granular casts (MBGC) on microscopic examination of urinary sediment (MicrExUrSed) are highly suggestive of ATI. We hypothesized that there is poor concordance between the presence of MBGC and FENa in ATI. Methods: We conducted a prospective observational study in patients with AKI seen during inpatient consultation. We extracted patients who underwent assessment of percentage of low power fields (LPFs) with MBGC by MicrExUrSed and concomitant measurement of FENa. Diagnostic concordance between MBGC and FENa and their individual prognostic value were examined. Results: Our cohort included 270 patients, 111 (41%) of whom were women. Median age was 61 years (range 27-92 years), and median serum creatinine was 3.7 mg/dl ( range1.2-22.0 mg/dl). MBGC were found in 49% (133/270). FENa <1% (inconsistent with ATI) was found in 50/133 (38%), 38/115 (33%), and 16/45 (36%) of those with >0%, ≥10%, and ≥50% LPFs with MBGC, respectively. Concordance between FENa and MBGC for ATI diagnosis was deemed fair (estimated κ-coefficient=0.2), and poor (κ=-0.11) within a subgroup of patients with preexisting chronic kidney disease (n=139). In patients with biopsy-proven ATI (n=49), MBGC had 100% specificity and 100% positive predictive value for ATI. MBGC were associated with greater risk for ≥50% increase in creatinine from baseline at discharge (acute kidney disease [AKD]). Conclusions: About two of five patients with MBGC identified by MicrExUrSed presented with FENa <1%. Presence of MBGC was consistent with ATI, as verified by biopsy, and were predictive of AKD. These data suggest that the sole reliance in low FENa to exclude ATI should be abandoned, and MicrExUrSed should be pursued for AKI diagnosis.

Refractoriness of Hyperkalemia and Hyperphosphatemia in Dialysis-Dependent AKI Associated with COVID-19.

Background: Persistent hyperkalemia (hyperK) and hyperphosphatemia (hyperP) despite renal replacement therapy (RRT) was anecdotally reported in COVID-19 and acute kidney injury (AKI) requiring RRT (CoV-AKI-RRT). However, observation bias could have accounted for the reports. Thus, we systematically examined the rate and severity of hyperK and hyperP in patients with CoV-AKI-RRT in comparison with the pre-COVID-19 era. Methods: We identified patients with CoV-AKI-RRT treated with sustained low-efficiency dialysis (SLED) for ≥2 days in March-April 2020. As pre-COVID-19 control, we included patients with AKI treated with SLED in December 2019. We examined the rates of hyperK (serum potassium [sK] ≥5.5 mEq/L), severe hyperK (sK ≥6.5 mEq/L), hyperP (serum phosphate [sP] ≥4.5 mg/dl), and moderate or severe hyperP (sP ≥7-10 and >10 mg/dl, respectively) as %SLED-days with an event. Results: Along the duration of SLED, the incidence of hyperK was greater in CoV-AKI-RRT (n=64; mean 19%±2% versus 14%±3% SLED-days, P=0.002) compared with control (n=60). The proportion of patients with one or more event of severe hyperK was greater in CoV-AKI (33% versus 7%, P<0.001). The incidence of hyperP was similar between groups (mean 56%±4% versus 53%±5% SLED-days, P=0.49). However, the proportion of patients with one or more event of moderate and severe hyperP was greater in CoV-AKI-RRT (86% versus 60%, P=0.001, and 50% versus 18%, P<0.001, respectively). Among those with CoV-AKI-RRT, sK and sP correlated with lactate dehydrogenase (LDH; r=0.31, P=0.04, and r=0.31, P=0.04, respectively), whereas hyperP also correlated with shorter SLED runs (hours/run; r=-0.27, P=0.05). Conclusions: Refractory hyperK and hyperP were more frequent in CoV-AKI-RRT compared with the pre-COVID-19 era. Because of the correlation of sK and sP with higher LDH and sP with shorter SLED runs, intracellular ion release from cell injury due to cytokine storm and RRT interruptions may account for the findings.