Can low lactate dehydrogenase be associated with kidney cancer?

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Low Lactate Dehydrogenase and Kidney Cancer

Low lactate dehydrogenase (LDH) is not typically associated with kidney cancer; rather, elevated LDH is a well-established poor prognostic marker in renal cell carcinoma (RCC). The question appears to be asking about the opposite of what occurs clinically.

LDH Elevation in Kidney Cancer

Elevated serum LDH is a recognized adverse prognostic factor in metastatic RCC and is incorporated into risk stratification models. 1 The Memorial Sloan-Kettering Cancer Center (MSKCC) prognostic model identifies elevated LDH as one of five risk factors for shortened survival in metastatic RCC, alongside low Karnofsky performance status, low hemoglobin, elevated corrected calcium, and time from diagnosis to therapy less than 1 year. 1

Prognostic Significance

  • High serum LDH levels correlate with poor overall survival in RCC patients. 2 In poor-risk metastatic RCC patients, those with LDH above the upper limit of normal had a hazard ratio for death of 2.81 compared to patients with normal LDH. 2

  • Elevated LDH predicts benefit from mTOR inhibitor therapy. 2 Among patients with elevated LDH, temsirolimus improved overall survival significantly (6.9 vs 4.2 months), whereas patients with normal LDH showed no significant survival benefit from temsirolimus versus interferon. 2

Tissue-Level LDH Expression

At the tissue level, clear cell RCC demonstrates characteristic alterations in LDH isoenzyme patterns, with increased LDHA expression associated with worse outcomes. 3, 4

  • LDHA overexpression correlates with larger tumor size, advanced clinical stage, higher histological grade, and shorter disease-free and overall survival. 3

  • Clear cell RCC typically shows a completely inverted LDH isoenzyme pattern (predominance of LDH-4 and LDH-5 rather than LDH-1 and LDH-2), reflecting a shift toward anaerobic glycolysis. 4 This inverted pattern was observed in 16 of 27 renal carcinomas studied, with 14 of these being clear cell type. 4

  • LDHB (which produces LDH-1) shows decreased expression in ccRCC and serves as an independent favorable prognostic marker. 5 Low LDHB expression correlates with poor overall survival, while high LDHB expression is protective. 5

Clinical Context

LDH is routinely measured as part of the laboratory workup for RCC patients. 1 The comprehensive metabolic panel for RCC evaluation includes LDH along with serum calcium, liver function studies, and serum creatinine. 1

Important Caveats

  • The question asks about LOW LDH, which is not a recognized clinical association with kidney cancer. If a patient with suspected or confirmed RCC has low LDH, this would actually be a favorable prognostic sign rather than a concerning finding.

  • LDH elevation reflects tumor burden, hypoxia, and anaerobic metabolism characteristic of aggressive RCC, particularly clear cell histology. 2, 4

  • Both serum LDH levels and tissue LDHA/LDHB expression patterns have independent prognostic value and may correlate with immune infiltration patterns in ccRCC. 5

References

1
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Dr.Oracle Medical Advisory Board & Editors, 2025

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