Jenabi MDAss. Professor of Medicineand Nephrology,iran University of medical Sciences Tehran , IranCHRONIC KIDNEY DISEASEIn the name of GOD
CHRONIC KIDNEY DISEASE
Chronic kidney disease (CKD) encompasses a spectrum of different pathophysiologic processes associated with abnormal kidney function, and a progressive decline in glomerular filtration rate (GFR).
IRREVERSIBLE LOSS OF GFR
DENOTES PROGRESSION EVEN WHEN THE UNDERLYING CAUSE HAS BEEN ELIMINATEDchronic renal failure
Why call it chronic kidney disease? why call it CKD as opposed to pre-ESRD, pre-dialysis or chronic renal failure ?Pre-ESRD gives the impression that dialysis is the inevitable outcome of all kidney diseases and that there are no effective therapies to retard its progression. It is the equivalent of referring to life as pre-death.The term renal failure also has a negative connotation and includes the term renal, which is not easily understood by patients and their families.
MOST OF THE CKD PATIENTS ARE ASYMPTOMATIC AND ARE DETECTED DURING SCREENING EITHER ROUTINE OR FOR UNRELATED ILLNESS
CKDESRDINCIDENCE OF CKDAt least 6% of the adult population in the USA has CKD at stages 1 and 2. An unknown subset of this group will progress to more advanced stages of CKD. An additional 4.5% of the U.S. population is estimated to have stages 3 and 4 CKD.
Uremia is a state of systemic poisoning
Due to cumulative effects of failure of many functions of kidneyESRD?
Pathophysiology of Chronic Kidney DiseaseTwo broad sets of mechanisms of damage: initiating mechanisms specific to the underlying etiology (immune complexes and mediators of inflammation in certain types of glomerulonephritis, or toxin exposure a set of progressive mechanisms, involving hyperfiltration and hypertrophy of the remaining viable nephrons
Pathophysiology of Chronic Kidney Disease 2why a reduction in renal mass from an isolated insult may lead to a progressive decline in renal function over many years?
Pathophysiology of Chronic Kidney Disease 3Increased intrarenal activity of the renin-angiotensin axis appears to contribute both to the initial adaptive hyperfiltration and to the subsequent maladaptive hypertrophy and sclerosis, the latter, in part, owing to the stimulation of transforming growth factor (TGF-).
CKD CausesCAUSE ADULTSCHILDREN
GLOMERULONEPHRITIS 3+ 4+
DIABETES 4+ RARE
HYPER TENSION 2+ RARE
POLYCYSTIC KIDNEY 2+ 1+
INTERSTITIAL NEPHRITIS 2+ 2+
OBSRUCTIVE NEPHROPATHY 1+ 3+
RENAL HYPOPLASIA RARE 2+
HEREDITARY DISORDERS RARE 1+
CKD Some DefinitionsCKD results when a disease process damages the structural or functional integrity of the kidney.This is clinically detected using either physical exam (hypertension), laboratory (hematuria, proteinuria, microalbuminuria) or imaging studies (CT, MRI, IVP or renal ultrasound).Almost all patients with a GFR 60 ml/min/1.73m2 have CKD.However, since GFR declines normally with age (approximately 1ml/min/1.73 m2 /year after age 20), a GFR between 60 - 90 ml/min/1.73m2 in the elderly may not be indicative of the presence of CKD.In order for patients to be classified as having CKD there must be some objective evidence on either physical exam, laboratory or imaging studies of kidney damage.
Estimate the Glomerular Filtration RateEstimates of the glomerular filtration rate (GFR) based on the serum creatinine have a high degree of correlation with determinations of GFR based on inulin (gold standard) or iothalamate clearances. The later are more accurate but are cumbersome and costly.These estimations also perform well when compared to collections of 24 hour urine which are difficult for patients to carry out and are often performed incorrectly.Cockcroft-Gault equation- [140-age(yr)] weight(kg)]/[72 serum Cr(mg/dl)] ( 0.85 for women).MDRD equation 7-170 [serum creatinine (mg/dl)] - 0.999 [age] - 0.176 [0.762 if pt is female ] **[1.180 if pt is black ] **[BUN (mg/dl)] - 0.170 [albumin (g/dl)] + 0.318.
Why can t one just use the serum creatinine ?The serum creatinine alone is not an accurate measure of glomerular filtration rate. Creatinine, unlike inulin, is secreted by renal tubules; and as renal function worsens the amount secreted increases. Normal ranges for serum creatinine are misleading because they do not take into account the age, sex, or weight of the patient.
Clinical examplesConsider the following two patients with identical serum Cr of 1.2 mg/ dL.Patient 1 - a 60 year old 50 kg woman Patient 2 - a 30 year old 90 kg man The first patient has a GFR of 39 ml/min/1.73 m2, which is markedly abnormal, while the second has a GFR of 115 ml/min/1.73 m2, well within the normal range.
CLASSIFICATION OF CKD-NKF
STAGEDESCRIPTIONGFR(ml/min)0WITH RISK FACTORS>90IKIDNEY DAMAGE (WITH NORMAL OR GFR)>90IIMILD60-89IIIMODERATE30-59IVSEVERE15-29VKIDNEY FAILURE
CKD deathComplicationsScreening for CKD risk factors:diabetes hypertensionage >60 family historyUS ethnic minoritiesCKD risk reduction; Screening for CKDDiagnosis & treatment; Treat comorbid conditions; Slow progressionEstimate progression; Treat complications; Prepare for replacementReplacement by dialysis & transplantNormalIncreased riskKidney failureDamage GFRConceptual Model for CKD
Albuminuria is also helpful for monitoring nephron injury apy in many forms of CKD While an accurate 24-h urine collection is the "gold standard" for measurement of albuminuria, the measurement of albumin-to-creatinine ratio in a spot first-morning urine sample is often more practical to obtain and correlates well. Persistence in the urine of >17 mg of albumin per gram of creatinine in males and 25 mg albumin per gram of creatinine in females usually signifies chronic renal damage. Microalbuminuria refers to the excretion of amounts of albumin too small to detect by urinary dipstick or conventional measures of urine protein. It is a good screening test for early detection of renal disease, in particular, and may be a marker for the presence of microvascular disease in general. Measurement of albuminuria
Pathophysiology and Biochemistry of UremiaThe uremic syndrome can be divided into manifestations in three spheres of dysfunction: (1) those consequent to the accumulation of toxins normally undergoing renal excretion, including products of protein metabolism. (2) those consequent to the loss of other renal functions, such as fluid and electrolyte homeostasis and hormone regulation. (3) progressive systemic inflammation and its vascular and nutritional consequencesHundreds of toxins that accumulate in renal failure have been implicated in the uremic syndrome; nitrogenous excretory products include guanido compounds, urates and hippurates, products of nucleic acid metabolism, polyamines, myoinositol, phenols, benzoates, and indoles
SYMPTOMS / SIGNSSYMPTOMS / SIGNSSYSTEMSYMPTOMSSIGNSGENERALFATIGUE, WELL BEINGWASTED,SALLOW COMPLEXIONSKIN ITCHING / BRUISINGPALLOR, PIGMENTATIONDRYNESSFROST, EXCORIATIONSGITANOREXIA / NAUSEAGI BLEEDVOMITING / HICCUPSCVSEDEMA, CHEST PAIN HT / CARDIOMEGALY DYSPNEARUB / CRACKLESMUSCULOBONE PAINDEFORMITIES / MYOPATHYSKELETALGROWTH FAILURENSNUMBNESS / CRAMPSNEUROPATHY / ASTERIXISINSOMNIA / IMPOTENCEMYOCLONUS / ACIDOSIS
Volume expansion (I)
Hyperphosphatemia (I)Fluid and electrolyte disturbances
Secondary hyperparathyroidism (I or P)Adynamic bone (D)Vitamin Ddeficient osteomalacia (I)Carbohydrate resistance (I)Hyperuricemia (I or P)Hypertriglyceridemia (I or P)Increased Lp(a) level (P)Decreased high-density lipoprotein level (P)Protein-energy malnutrition (I or P)Impaired growth and development (P)Infertility and sexual dysfunction (P)Amenorrhea (I/P)2-Microglobulin associated amyloidosis (P or D)Endocrine-metabolic disturbances
Bone Manifestations of CKD
Flowchart for the development of bone, phosphate, and calcium abnormalities
Recent epidemiologic evidence has shown a strong association between hyperphosphatemia and increased cardiovascular mortality in patients with stage 5 CKD and even in patients with earlier stages of CKDHyperphosphatemia and hypercalcemia are associated with increased vascular calcificationCalcium, Phosphorus, and the Cardiovascular System
Fibroblast growth factor 23 (FGF-23) is part of a family of phosphatonins that promotes renal phosphate excretion. Recent studies have shown that levels of this hormone, secreted by osteocytes, increases early in the course of CKD. It may defend normal serum phosphorus in at least three ways: (1) increased renal phosphate excretion; (2) stimulation of PTH, which also increases renal phosphate excretion; and (3) suppression of the formation of 1,25(OH)2D3, leading to diminished phosphorus absorption from the gastrointestinal tract. Interestingly, high levels of FGF-23 are also an independent risk factor for left ventricular hypertrophy and mortality in dialysis patients. Moreover, elevated levels of FGF-23 may indicate the need for therapeutic intervention (e.g., phosphate restriction), even when serum phosphate levels are within the normal range.
Calciphylaxis is a devastating condition seen almost exclusively in patients with advanced CKDthere is evidence of vascular occlusion in association with extensive vascular calcification:advanced hyperparathyroidismincreased use of oral calcium