MEDICAL RESEARCH BLOG
KREBS CYCLE METABOLITES
CASE STUDY | CGZ
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62-year-old male
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Weight: 141 kg (approximately double that of an average adult patient weighing 79 kg)
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Height: 1.8 meters
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BMI: 43
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15-year history of Type 2 Diabetes Mellitus (T2DM) and Hypertension, under treatment with insulin glargine, telmisartan 40 mg once daily, and diltiazem 180 mg once daily.
After two years of prior treatment for chronic kidney disease, by December 2015 his laboratory values were as follows:
Urea: 206.8 mg/dL | Creatinine: 6.4 mg/dL | eGFR: 8.5 mL/min | Hemoglobin: 9.7 g/dL | Uric acid: 15 mg/dL | Proteinuria: 150 mg/dL
At that point, the patient was advised to initiate hemodialysis. However, he declined, and conservative treatment with Krebs Cycle intermediate metabolites was initiated.
As shown in the data, after one month, urea decreased from 206 to 107 mg/dL; the following month it decreased further to 100 mg/dL; and after one year, the final value was 180 mg/dL. Regarding creatinine, it began at 6.4 mg/dL (corresponding to an eGFR of 8.5 mL/min prior to treatment with Krebs metabolites) and, after one year, decreased to 5.8 mg/dL, with a corresponding eGFR of 9.5 mL/min.
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Medications: Omeprazole, erythropoietin, testosterone, folic acid, vitamin B complex, telmisartan, atenolol, aspirin, allopurinol, furosemide, polyethylene glycol every 3 weeks, and metronidazole every 3 weeks.
CASE STUDY | VSL
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60-year-old female
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Weight: 87 kg
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Height: 1.62 meters
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Diagnosis: Granulomatosis with polyangiitis (Wegener’s), C-ANCA positive and P-ANCA negative, with a C-reactive protein of 90, and both pulmonary and renal involvement.
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Baseline (pre-treatment with Krebs Cycle intermediate metabolites):
Urea: 109 mg/dL | Creatinine: 2.7 mg/dL | eGFR (CKD-EPI): 18.4 mL/min | Hemoglobin: 10 g/dL
Long-acting erythropoietin (EPO) therapy was initiated, and the patient was informed that she would likely become a candidate for hemodialysis in the coming months. Treatment with Krebs Cycle intermediate metabolites was then started.
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After 5 months of treatment:
Urea: 28 mg/dL | Creatinine: 2.1 mg/dL | eGFR: 25 mL/min
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Two years later (May 2014):
Urea: 71 mg/dL | Creatinine: 2.6 mg/dL | eGFR: 19.3 mL/min
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Eight years after continuous treatment (January 2020):
Urea: 160 mg/dL | Creatinine: 5.3 mg/dL | eGFR: 8.3 mL/min
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February 2020:
Treatment with Krebs metabolites had been discontinued for one month due to gastrointestinal intolerance. Laboratory values were:
Urea: 225 mg/dL | Creatinine: 5.5 mg/dL | eGFR: 7.9 mL/min
At the end of February 2020, hemodialysis was initiated (3 sessions per week, 3 hours each), and the patient remained on dialysis for 2.5 years. She ultimately passed away with a hemoglobin level of 6 g/dL and heart failure.
- Clinical significance:
This case has not been previously reported in the medical literature. Starting from baseline values of eGFR 18.4 mL/min, creatinine 2.7 mg/dL, and urea 109 mg/dL, after 8 years of conservative treatment, final values were eGFR 8.3 mL/min, creatinine 5.3 mg/dL, and urea 160 mg/dL, representing an average decline in eGFR of 1.26 mL/min per year.
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Medications: Erythropoietin (EPO), iron dextran, folic acid, vitamin B complex, calcitriol, valsartan, verapamil, furosemide, allopurinol, sulodexide.
For granulomatosis: induction therapy with cyclophosphamide, as well as co-trimoxazole, deflazacort, azathioprine, and mycophenolate mofetil.
CASE STUDY | VGC
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87-year-old male
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Occupation: Agriculture and livestock farming
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Medical history: 15-year history of hypertension; 40-year history of knee osteoarthritis (gonarthrosis)
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Initial blood pressure: 210/90 mmHg
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Imaging findings:
Chest CT scan showing signs of pulmonary hypertension
Echocardiogram revealing concentric left ventricular hypertrophy
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Clinical course:
After one year of treatment (June 2016 to July 2017), eGFR improved from an initial 8.5 mL/min to 19.1 mL/min (an increase of 10.6 mL/min over the first year), with corresponding creatinine and urea levels of 2.8 mg/dL and 63.6 mg/dL, respectively.
After 35 months, creatinine evolved from a pre-treatment value of 5.5 mg/dL to 5.0 mg/dL, with an eGFR of 9.4 mL/min and urea of 104 mg/dL.
The last recorded urea value was 124 mg/dL after 40 months of treatment and follow-up.
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Clinical significance:
This case highlights the multiple benefits of treatment with Krebs Cycle intermediates. Medical literature reports a survival of no more than 6 months once serum creatinine reaches levels of approximately 5 mg/dL, with a corresponding eGFR of around 8 mL/min, unless dialysis is initiated. Even then, the average survival in patients of this advanced age (around 90 years) is approximately 12 months.
CASE STUDY | ARA
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67-year-old female
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Weight: 62 kg
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Height: 1.45 meters
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Medical history:
12-year history of Type 2 Diabetes Mellitus, treated with insulin glargine 14 units/day
11-year history of hypertension, previously treated with losartan 50 mg twice daily
Diagnosed with chronic kidney disease (CKD) 4 years prior, secondary to nephroangiosclerosis
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Imaging findings:
Renal ultrasound showed loss of corticomedullary differentiation.
Right kidney volume: 60 cc
Left kidney volume: 49 cc
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The patient had been under regular nephrology care for 4 years. By September 2022, due to the following laboratory values:
Urea: 192 mg/dL | Creatinine: 3.56 mg/dL | Hemoglobin: 10.9 g/dL | eGFR (CKD-EPI): 13.6 mL/min
She was advised that she was a candidate for timely initiation of renal replacement therapy (RRT), which she declined.
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In September 2022, conservative treatment with Krebs Cycle intermediate metabolites was initiated, in addition to medications prescribed by the nephrology service at IMSS: Erythropoietin (EPO), Folic acid, Vitamin B complex, Ferrous sulfate, Atorvastatin, Insulin glargine (14 units), Furosemide, and Telmisartan 40 mg.
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Clinical course (22 months of conservative treatment):
Baseline: Creatinine: 3.56 mg/dL | eGFR: 13.6 mL/min | Urea: 192 mg/dL
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As of June 11, 2024:
Creatinine: 2.58 mg/dL | eGFR: 19.8 mL/min | Urea: 104 mg/dL | Hemoglobin: 11.1 g/dL
Erythropoietin had been discontinued for 6 months. The patient reports being asymptomatic and able to carry out all daily activities.
CASE STUDY | NED
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86-year-old male patient
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Medical history:
History of skin carcinoma of the left forearm 10 years prior, with metastasis to the left axillary lymph nodes, treated with chemotherapy. Daily use of rabeprazole for the past 10 years. No other significant medical history
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Baseline (October 2021):
Creatinine: 1.98 mg/dL | eGFR (CKD-EPI): 32.3 mL/min
Treatment with Krebs Cycle intermediate metabolites was initiated.
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Clinical course:
As shown in the data:
After 2 months of treatment, creatinine decreased to 1.52 mg/dL
After 5 months (March 24, 2022), creatinine was 1.6 mg/dL, with an eGFR of 41.4 mL/min, compared to 32.3 mL/min pre-treatment
During the same period, hemoglobin increased from 12.6 to 13.7 g/dL
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Follow-up (May 2024):
At 89 years of age, after 31 months of treatment with Krebs metabolites: Creatinine: 1.5 mg/dL | eGFR: 44.2 mL/min
Despite being 3 years older, the patient’s eGFR increased by 11.9 mL/min compared to baseline.
