1) The presence of markers of kidney damage for greater than 3 months in blood, urine, or on imaging
a) e.g proteinuria, non-urological hematuria, polycystic kidney disease, horseshoe kidney, etc.
or
2) The presence of a GFR of less than 60 mL/min/1.73m2 for more than 3 months
Risk Factors
The most common cause of end-stage kidney (ESKD) disease is diabetes (44%), followed by hypertension (29%). The cause is usually from an increase in intraglomerular pressure which is damaging to the glomerular filtering capabilities. Other risk factors include a family history of CKD, autoimmune disease (e.g. SLE, vasculitis, scleroderma), HIV, Hepatitis B or C, amyloidosis, obstructive nephropathy from recurrent UTI or nephrolithiasis, and certain medications (analgesics, immune
suppressants, HIV medications). Acute kidney injuries may also
contribute to CKD, particularly if requiring inpatient dialysis. Recent evidence suggests pediatric kidney disease may also be associated with adult ESKD.
suppressants, HIV medications). Acute kidney injuries may also
contribute to CKD, particularly if requiring inpatient dialysis. Recent evidence suggests pediatric kidney disease may also be associated with adult ESKD.
Staging and Estimating GFR
Staging CKD is most frequently done by calculating the estimated glomerular function rate (eGFR) as a proxy for kidney function. These calculations are often based on a patient’s serum creatinine (a muscle metabolite that is filtered in the kidney). Of the three most common calculators (CKD-EPI, MDRD, Cockroft-Gault equation), the CKD-EPI is the most accurate at predicting mortality and ESKD and generally is what is recommended for use. (of note- many dose adjustment for drugs still use Cockroft-Gault- look carefully at this when looking at dose adjustments).
Link to CKD-EPI calculator found here: http://nephromatic.com/egfr.php
After calculating the eGFR, CKD can be staged into 1 of 5 stages. Using the GFR clock is one way to remember the eGFR cut-offs for each CKD stage.
Link to GFR clock from Malvinder Parma.
Because the above calculators rely on creatinine (which can vary in patients with extreme muscle mass e.g. sarcopenic patients such as the frail elderly or sarco-full patients such as body-builders), creatinine clearance can also be estimated and used to stage CKD. 24-hour urine creatinine clearance equation works for all patients regardless of size. Creatinine clearance is based on the ratio of urine creatinine and plasma creatinine.
CrCl = Urine Cr (mg/dl) * Urine volume (ml)] / [Plasma Cr (mg/dl) * Time (min)
CrCl calculator: http://www-users.med.cornell.edu/~spon/picu/calc/crclcalc.htm
Cystatin C is another biomarker that can be used for estimated eGFR. Like creatinine clearance, it is mostly useful in patients where creatinine is a bad estimate, though may also help provide more accurate kidney function estimates when combined with above calculations.
CKD Staging is also based on the level of proteinuria seen in the patient. If there is proteinuria or greater than 300mg albumin/mg/g Cr in a urine protein:creatinine ratio, then the proteinuria is staged as A3. If between 30-300 (microalbuminuria), the staging is A2. A1 is if there is no significant
proteinuria or microalbuminuria.
proteinuria or microalbuminuria.
Prognosis
TheeGFR and proteinuria offers a general prognosis as demonstrated in the Heat Map.
With an estimated GFR and knowledge of proteinuria, the risk of kidney failure requiring dialysis or transplant can be calculated using a Kidney Failure Risk calculator based on Tangri et al, JAMA 2016. More generally,
a lower eGFR has an observed association with the risk of death, cardiovascular events, and hospitalization.
a lower eGFR has an observed association with the risk of death, cardiovascular events, and hospitalization.
Initial Work-up
Recommended workup for newdiagnosis of CKD:
● Serum electrolytes for eGFR and electrolyte
abnormalities (e.g. metabolic acidosis)
abnormalities (e.g. metabolic acidosis)
● Complete Blood Cell Count (Anemia)
● Lipid profile
● Uric Acid
● Serum albumin
● Kidney ultrasound
○ to look for hydronephrosis, obstruction, cysts,
stones, and assess kidney size and characterization
stones, and assess kidney size and characterization
● Urinalysis
○ Quantify proteinuria with urine protein-to-creatinine ratio (Urine albumin-to-creatinine will miss multiple myeloma Bence-Jones proteins)
○ Look for hematuria or other signs of glomerulonephritis
● Consider kidney biopsy if significant proteinuria and no history of diabetes (or other factors)
In patients with CKD G3 (eGFR less than 60 mL.min):
● Serum calcium, phosphorus, PTH, Vitamin D to
assess for Bone Mineral Disease
assess for Bone Mineral Disease
If suggested by the history and physical examination and UA:
● Antinuclear antibody testing to evaluate for
lupus
lupus
● Hepatitis B and C, and HIV serology
● Serum antineutrophil cytoplasmic antibodies to
evaluate for ANCA-associated vasculitis
evaluate for ANCA-associated vasculitis
● Serum and urine protein immunoelectrophoresis to
test for multiple myeloma. Free serum light chains.
test for multiple myeloma. Free serum light chains.
Monitoring
All patients with at least CKD G4 disease (GFR ≤30 mL/min/1.73 m2 )
should establish care with a nephrologist. Consultation is also
recommended if proteinuria greater than 3g / 24 hr, evidence of glomerulonephritis (hematuria, proteinuria, and hypertension), an eGFR decline of 50% within 1 year.
should establish care with a nephrologist. Consultation is also
recommended if proteinuria greater than 3g / 24 hr, evidence of glomerulonephritis (hematuria, proteinuria, and hypertension), an eGFR decline of 50% within 1 year.
General management should also prioritize treatment of the underlying condition (e.g. hypertension and diabetes) to reverse the progression of CKD.
Management
Medications
ACE-inhibitors demonstrate a significant reduction in progression of CKD and reduction in proteinuria per the RENAAL, IDNT, and other trials. Fewer patients had progression to ESKD though a mortality benefit was not observed.
Of note, ACE-inhibitors or ARBs (RAAS blockade) are likely to cause a benign increase in serum creatinine. In general, if the creatinine bump greater than 30%, RAAS blockade should be discontinued. An increase in creatinine after ACE-I may show greatest risk of mortality (though it is
unclear what would happen if the patients with bumps were not on ACE-I, so this is not an indication to necessarily discontinue therapy).
unclear what would happen if the patients with bumps were not on ACE-I, so this is not an indication to necessarily discontinue therapy).
Blood
Pressure Treatment
Pressure Treatment
Per KDOQI 2012 guidelines, target blood pressure in CKD is less than 130 over 80 mm Hg. With ACE-inhibitors being the first line drug.
Diabetes
Control
Control
Metformin: if eGFR 30-45 and already on metformin (and this is not AKI) can continue metformin. Do not start NEW if eGFR is 30-45, but ok if higher than 45.
SGLT2 inhibitors
(i.e. Empagliflozin and Canagliflozin) are associated with lower rates of
worsening nephropathy, progression to macroalbuminuria, initiation of renal replacement therapy and mortality. (EMPA-Reg, EMPA-Reg ESRD + CANVAS). However, studies demonstrating their effectiveness in CKD are ongoing.
(i.e. Empagliflozin and Canagliflozin) are associated with lower rates of
worsening nephropathy, progression to macroalbuminuria, initiation of renal replacement therapy and mortality. (EMPA-Reg, EMPA-Reg ESRD + CANVAS). However, studies demonstrating their effectiveness in CKD are ongoing.
Bone
Mineral Disease Screening
Mineral Disease Screening
All patients with CKD G4 should be screened for secondary and tertiary
hyperparathyroidism. The screening labs are a PTH, phosphorus, calcium and vitamin D level. Further information can be found at the KDIGO guidelines on BMD.
hyperparathyroidism. The screening labs are a PTH, phosphorus, calcium and vitamin D level. Further information can be found at the KDIGO guidelines on BMD.
Depression
Screening
Screening
Depression affects approximately 20% of all patients with CKD.
Anemia
There are multiple causes of anemia in patients with CKD including iron
deficiency. KDIGO recommends intravenous iron for anemic, nondialysis, patients with CKD with transferrin saturation link here.
deficiency. KDIGO recommends intravenous iron for anemic, nondialysis, patients with CKD with transferrin saturation link here.
Nutrition
Guidelines remain controversial but a full discussion can be found at the AKJD Blog or in the recent NEJM Review.
Medications to Avoid
Bactrim- Use of Bactrim (trimethoprim-sulfamethoxazole) was associated with 3 excess cardiac deaths per 1,000 prescriptions presumably due to hyperkalemia (e.g. patients with CKD are higher risk)
Baclofen– should be avoided in ESKD or eGFR less than 30 and dose reduced with eGFR between 30-6o.
Proton Pump Inhibtors
Observational data demonstrates a link between proton pump inhibitors
and CKD.
and CKD.
Kidney function dosed medications
Certain medications, such as gabapentin, also will require adjustment for dosing based on kidney function.
Contrast?
Contrast-induced kidney injury (CIN) may be overestimated in literature. The AMACING trial shows that pre-hydration does not reduce kidney injury in those exposed to contrast.
NSAIDS?
Patients with CKD depend on prostaglandins for vasodilation of afferent
arterioles and renal blood flow. NSAIDs block prostaglandin activity and
can cause acute kidney injury. KDIGO guidelines recommend avoiding NSAIDS in patients with CKD, but the evidence suggests that risk of NSAID use in CKD patients is pretty low: The Male Physician Study showed no
elevation in serum creatinine with consistent NSAID use. However, the PRECISION Trial showed only ~1% risk of kidney events in CKD patients with daily high-dose NSAIDs.
arterioles and renal blood flow. NSAIDs block prostaglandin activity and
can cause acute kidney injury. KDIGO guidelines recommend avoiding NSAIDS in patients with CKD, but the evidence suggests that risk of NSAID use in CKD patients is pretty low: The Male Physician Study showed no
elevation in serum creatinine with consistent NSAID use. However, the PRECISION Trial showed only ~1% risk of kidney events in CKD patients with daily high-dose NSAIDs.
For a more succinct review of the above, check out the new ClinicWiki page on Chronic Kidney Disease.
Post written by
Justin Berk, MD, MPH @justinberk
Med-Peds Resident, John
Hopkins University
Hopkins University
NSMC Intern 2018
An incredibly informative and concise resource! As a primary care provider, this ‘Cheat Sheet’ is like a valuable gem in the realm of managing Chronic Kidney Disease. Thank you for simplifying such a complex topic and helping us provide better care to our patients.
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