View source for Chronic renal failure

'''For patient information click [[{{PAGENAME}} (patient information)|here]]'''

{{Infobox_Disease |
  Name           = {{PAGENAME}} |
  Image          = |
  Caption        = |
  DiseasesDB     = |
  ICD10          = N18 |
  ICD9           = {{ICD9|585}} |
  ICDO           = |
  OMIM           = |
  MedlinePlus    = |
 }}

{{SI}}

{{CMG}}; '''Associate Editor(s)-In-Chief:''' {{CZ}}

==Overview==
'''Chronic renal failure''' (CRF), also known as '''chronic kidney failure''' (CKF) or '''chronic kidney disease''' (CKD), or '''chronic renal insufficiency''' (CRI) is a slowly progressive loss of [[renal function]] over a period of months or years, and defined as an abnormally low [[glomerular filtration rate]], which is usually determined indirectly by the [[creatinine]] level in blood serum.

CRF that leads to severe illness and requires some form of renal replacement therapy (such as [[dialysis]]) is called '''end-stage renal disease''' (ESRD).

==Signs and symptoms==
Initially it is without specific symptoms and can only be detected as an increase in serum [[creatinine]]. As the [[kidney]] function decreases:
* [[Blood pressure]] is increased due to fluid overload and production of vasoactive hormones leading to [[hypertension]] and [[congestive heart failure]]
* [[Urea]] accumulates, leading to [[azotemia]] and ultimately [[uremia]] (symptoms ranging from lethargy to [[pericarditis]] and [[encephalopathy]])
* [[Potassium]] accumulates in the blood (known as [[hyperkalemia]] with symptoms ranging from [[malaise]] to fatal [[cardiac arrhythmia]]s)
* [[Erythropoietin]] synthesis is decreased (leading to [[anemia]] causing [[fatigue (physical)|fatigue]])
* [[Fluid balance|Fluid volume overload]] - symptoms may range from mild [[edema]] to life-threatening [[pulmonary edema]]
* [[Hyperphosphatemia]] - due to reduced phosphate excretion, associated with [[hypocalcemia]] (due to [[vitamin D3]] deficiency).
** Later this progresses to [[tertiary hyperparathyroidism]], with [[hypercalcaemia]], [[renal osteodystrophy]] and vascular calcification
* [[Metabolic acidosis]], due to decreased generation of [[bicarbonate]] by the kidney, leads to uncomfortable breathing and further worsening of bone health.

CRF patients suffer from accelerated [[atherosclerosis]] and have higher incidence of [[cardiovascular disease]], with a poorer prognosis.

==Diagnosis==
In many CRF patients, previous renal disease or other underlying diseases are already known. A small number presents with CRF of unknown cause. In these patients, a cause is occasionally identified retrospectively.  

It is important to differentiate CRF from [[acute renal failure]] (ARF) because ARF can be reversible. Abdominal [[medical ultrasonography|ultrasound]] is commonly performed, in which the size of the [[kidney]]s are measured.  Kidneys in CRF are usually smaller (< 9 cm) than normal kidneys with notable exceptions such as in [[diabetic nephropathy]] and [[polycystic kidney disease]].  Another diagnostic clue that helps differentiate CRF and ARF is a gradual rise in serum creatinine (over several months or years) as opposed to a sudden increase in the serum creatinine (several days to weeks). If these levels are unavailable (because the patient has been well and has had no blood tests) it is occasionally necessary to treat a patient briefly as having ARF until it has been established that the renal impairment is irreversible.

Numerous uremic toxins (see link) are accumulating in chronic renal failure patients treated with standard dialysis. These toxins show various cytotoxic activities in the serum, have different molecular weights and some of them are bound to other proteins, primarily to albumin. Such toxic protein bound substances are receiving the attention of scientists who are interested in improving the standard chronic dialysis procedures used today.

==Causes==
===Common Causes===

===Causes by Organ System===
{|style="width:80%; height:100px" border="1"
|style="height:100px"; style="width:25%" border="1" bgcolor="LightSteelBlue" | '''Cardiovascular'''
|style="height:100px"; style="width:75%" border="1" bgcolor="Beige" |[[Malignant hypertension]], [[Systemic hypertension]]
|-
|-bgcolor="LightSteelBlue"
| '''Chemical / poisoning'''
|bgcolor="Beige"| [[Lead]], [[Nitrosourea compounds]], [[Pentamidine]], [[Radiocontrast agents]]
|-
|-bgcolor="LightSteelBlue"
| '''Dermatologic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Drug Side Effect'''
|bgcolor="Beige"|[[Acetominophen]], [[Acyclovir ]], [[Allopurinol]], [[Aminoglycosides]], [[Analgesic abuse]], [[Angiotensin-converting enzyme inhibitors]], [[Anti-coagulants]], [[Aspirin]], [[bevacizumab]], [[Bismuth]], [[Carboplatin]], [[Carbon tetrachloride]], [[Carmustine]], [[Celecoxib]], [[Chloroquine]], [[Cimetidine]], [[Cyclosporine]], [[Erythromycin]], [[Esomeprazole ]], [[Foscarnet]], [[Gentamicin]], [[Hydroxychloroquine]], [[Ibuprofen]], [[Indinavir]], [[Infliximab ]], [[Isoniazid]], [[Lansoprazole ]], [[Lithium]], [[Lomustine]], [[Methicillin]], [[Mitomycin C]], [[Naproxen]], [[Interferons]], [[Omeprazole ]], [[Pamidronate]], [[Pantoprazole ]], [[Penicillin-like drugs]], [[Phenytoin ]], [[Propylthiouracil]], [[Quinine]], [[Rabeprazol]], [[Rifampicin]], [[Sickle cell disease ]], [[Sulfa-containing antibiotics]], [[Sulfonamides]], [[Tacrolimus]], [[Tenofovir]], [[Trimethadione ]], [[Vancomycin]]
|-
|-bgcolor="LightSteelBlue"
| '''Ear Nose Throat'''
|bgcolor="Beige"| No underlying causes
|- 
|-bgcolor="LightSteelBlue"
| '''Endocrine'''
|bgcolor="Beige"| No underlying causes
|- 
|-bgcolor="LightSteelBlue"
| '''Environmental'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Gastroenterologic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Genetic'''
|bgcolor="Beige"| [[Alport's syndrome]], [[Balkan endemic nephropathy]], [[Adenine phosphoribosyltransferase deficiency]], [[Alström syndrome]], [[Barakat syndrome]], [[Bardet-Biedl syndrome]], [[Fabry's Disease]], [[Hereditary Nephritis]], [[Lecithin cholesterol acyltransferase deficiency]], [[Lesch-Nyhan syndrome]], [[Loken Senior syndrome]], [[Lowe syndrome]], [[Nail-Patella Syndrome]], [[Papillorenal syndrome]], [[Polycystic kidney disease]], [[Townes-Brocks syndrome]], [[X-linked recessive nephrolithiasis type 1]], [[Vesico-uretero-renal reflux]], [[X-linked hypophosphatemia]]
|-
|-bgcolor="LightSteelBlue"
| '''Hematologic'''
|bgcolor="Beige"|[[Acute intermittent porphyria]], [[Light chain disease]], [[Myeloma]], [[Normocytic normochromic anemia]], [[Renal vein thrombosis]], [[Thrombotic thrombocytopenic purpura]]
|-
|-bgcolor="LightSteelBlue"
| '''Iatrogenic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Infectious Disease'''
|bgcolor="Beige"|[[Chronic pyelonephritis]], [[Schistosoma haematobium]], [[Tuberculosis]]
|-
|-bgcolor="LightSteelBlue"
| '''Musculoskeletal / Ortho'''
|bgcolor="Beige"|[[Idiopathic multicentric osteolysis]]
|-
|-bgcolor="LightSteelBlue"
| '''Neurologic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Nutritional / Metabolic'''
|bgcolor="Beige"|[[Calcium phosphate deposition]], [[cystinosis]], [[Diabetic nephropathy]], [[Fabry's disease]], [[Hyperkalemia]], [[Hyperlipidemia]], [[Hyperoxaluria]], [[Hyperphosphatemia]], [[Metabolic acidosis]], [[Oxalosis]], [[X-linked hypophosphatemia]]
|-
|-bgcolor="LightSteelBlue"
| '''Obstetric/Gynecologic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Oncologic'''
|bgcolor="Beige"| [[Metastatic prostate cancer]]
|-
|-bgcolor="LightSteelBlue"
| '''Opthalmologic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Overdose / Toxicity'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Psychiatric'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Pulmonary'''
|bgcolor="Beige"|[[Goodpasture’s syndrome]]
|-
|-bgcolor="LightSteelBlue"
| '''Renal / Electrolyte'''
|bgcolor="Beige"| [[Analgesic nephritis]], [[Alport's syndrome]], [[Balkan endemic nephropathy]], [[Chronic Glomerulonephritis]], [[Chronic Pyelonephritis]], [[Congenital Nephrotic Syndrome]], [[Diabetic nephropathy]], [[Goodpasture’s syndrome]], [[Focal glomerulosclerosis]], [[Glomerulosclerosis]], [[Hypertensive nephrosclerosis ]], [[Hereditary Nephritis]], [[Idiopathic membranous nephropathy]], [[IgA nephropathy]], [[Interstitial Nephritis]],  [[Lupus nephritis]], [[Papillorenal syndrome]], [[Polycystic kidney disease]],[[Medullary cystic renal disease]], [[Medullary sponge kidney]], [[Membranoproliferative Glomerulonephritis (MPGN)]], [[Membranous nephropathy]], [[Nephrolithiasis]], [[Nephrosclerosis]], [[Obstructive uropathy]], [[Proteinuria]], [[Reflux nephropathy]], [[Renal artery stenosis]], [[Type IV renal tubular acidosis]], [[Vesicoureteral reflux]], [[Xanthogranulomatous pyelonephritis]], [[Vesico-uretero-renal reflux]]
|-
|-bgcolor="LightSteelBlue"
| '''Rheum / Immune / Allergy'''
|bgcolor="Beige"|[[Goodpasture’s syndrome]], [[Lupus nephritis]], [[Rheumatoid arthritis]], [[Scleroderma]], [[Systemic Lupus Erythematosus]], [[Systemic sclerosis]], [[Vasculitis]], [[Wegener's granulomatosis]]
|-
|-bgcolor="LightSteelBlue"
| '''Sexual'''
|bgcolor="Beige"| [[Benign prostatic hyperplasia]], [[Denys-Drash syndrome]], [[Metastatic prostate cancer ]]
|-
|-bgcolor="LightSteelBlue"
| '''Trauma'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Urologic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Dental'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Miscellaneous'''
|bgcolor="Beige"|[[Amyloidosis]], [[Chronic inflammation]], [[Hemolytic uremic syndrome]]
 
|-
|}

===Causes in Alphabetical Order=== 
{{MultiCol}}
*[[Acetominophen]]
*[[Acute intermittent porphyria]]
*[[Acyclovir ]]
*[[Adenine phosphoribosyltransferase deficiency]]
*[[Allopurinol]]
*[[Alport's syndrome]]
*[[Alström syndrome]]
*[[Aminoglycosides]]
*[[Amyloidosis]]
*[[Analgesic nephritis]]
*[[Angiotensin-converting enzyme inhibitors]]
*[[Anti-coagulants]]
*[[Aspirin]]
*[[Balkan endemic nephropathy]]
*[[Barakat syndrome]]
*[[Bardet-Biedl syndrome]]
*[[Benign prostatic hyperplasia]]
*[[Bevacizumab]]
*[[Bismuth]]
*[[Calcium phosphate deposition]]
*[[Carbon tetrachloride ]]
*[[Carboplatin]]
*[[Carmustine]]
*[[Celecoxib]]
*[[Chloroquine]]
*[[Chronic Glomerulonephritis]]
*[[Chronic inflammation]]
*[[Chronic Pyelonephritis]]
*[[Cimetidine]]
*[[Congenital Nephrotic Syndrome]]
*[[Cyclosporine]]
*[[Cystinosis]]
*[[Denys-Drash syndrome]]
*[[Diabetic nephropathy]]
*[[Erythromycin]]
*[[Esomeprazole ]]
*[[Fabry's Disease]]
*[[Focal glomerulosclerosis]]
*[[Foscarnet]]
*[[Gentamicin]]
*[[Glomerulosclerosis]]
*[[Goodpasture’s syndrome]]
*[[Hemolytic uremic syndrome]]
*[[Hereditary Nephritis]]
*[[Hydroxychloroquine]]
*[[Hyperkalemia]]
*[[Hyperlipidemia]]
*[[Hyperoxaluria]]
*[[Hyperphosphatemia]]
*[[Hypertensive nephrosclerosis ]]
*[[Ibuprofen]]
*[[Idiopathic membranous nephropathy]]
*[[Idiopathic multicentric osteolysis]]
*[[IgA nephropathy]]
*[[Indinavir]]
*[[Infliximab ]]
*[[Interstitial Nephritis]]
*[[Isoniazid]]
*[[Jeune's thoracic dystrophy syndrome]]
*[[Lansoprazole ]]
*[[Lead]]
*[[Lecithin cholesterol acyltransferase deficiency]]
*[[Lesch-Nyhan syndrome]]
*[[Light chain disease]]
*[[Lithium]]
{{ColBreak}}
*[[Loken Senior syndrome]]
*[[Lomustine]]
*[[Lowe syndrome]]
*[[Lupus nephritis]]
*[[Malignant hypertension]]
*[[Medullary cystic renal disease]]
*[[Medullary sponge kidney]]
*[[Membranoproliferative Glomerulonephritis (MPGN)]]
*[[Membranous nephropathy]]
*[[Metabolic acidosis]]
*[[Metastatic prostate cancer ]]
*[[Methicillin]]
*[[Mitomycin C]]
*[[Myeloma]]
*[[Nail-Patella Syndrome]]
*[[Naproxen]]
*[[Nephrolithiasis]]
*[[Nephrosclerosis]]
*[[Nitrosourea compounds]]
*[[Normocytic normochromic anemia]]
*[[Interferons]]
*[[Obstructive uropathy]]
*[[Omeprazole ]]
*[[Oxalosis]]
*[[Pamidronate]]
*[[Pantoprazole ]]
*[[Papillorenal syndrome]]
*[[Penicillin-like drugs]]
*[[Pentamidine]]
*[[Phenytoin ]]
*[[Polycystic kidney disease]]
*[[Propylthiouracil]]
*[[Proteinuria]]
*[[Pyelonephritis, chronic]]
*[[Quinine]]
*[[Rabeprazol]]
*[[Radiocontrast agents]]
*[[Reflux nephropathy]]
*[[Renal artery stenosis]]
*[[Renal vein thrombosis]]
*[[Rheumatoid arthritis]]
*[[Rifampicin]]
*[[Schistosoma haematobium]]
*[[Scleroderma]]
*[[Sickle cell disease ]]
*[[Sulfa-containing antibiotics]]
*[[Sulfonamides]]
*[[Systemic hypertension]]
*[[Systemic Lupus Erythematosus]]
*[[Systemic sclerosis]]
*[[Tacrolimus]]
*[[Tenofovir]]
*[[Thrombotic thrombocytopenic purpura]]
*[[Townes-Brocks syndrome]]
*[[Trimethadione ]]
*[[Tuberculosis]]
*[[Type IV renal tubular acidosis]]
*[[Vancomycin]]
*[[Vasculitis]]
*[[Vesicoureteral reflux]]
*[[Vesico-uretero-renal reflux, congenital]]
*[[Wegener's granulomatosis]]
*[[Xanthogranulomatous pyelonephritis]]
*[[X-linked hypophosphatemia]]
*[[X-linked recessive nephrolithiasis type 1]]
{{EndMultiCol}}



The most common causes of CRF are [[diabetic nephropathy]], [[hypertension]], and [[glomerulonephritis]].  Together, these cause approximately 75% of all adult cases. Certain geographic areas have a high incidence of HIV nephropathy. 

Historically, kidney disease has been classified according to the part of the renal anatomy that is involved, as:
* Vascular, includes large vessel disease such as bilateral [[renal artery stenosis]] and small vessel disease such as ischemic nephropathy, [[hemolytic-uremic syndrome]] and [[vasculitis]]
* Glomerular, comprising a diverse group and subclassified into 
** Primary Glomerular disease such as [[focal segmental glomerulosclerosis]] and [[IgA nephropathy]]
** Secondary Glomerular disease such as [[diabetic nephropathy]] and [[lupus nephritis]]
* Tubulointerstitial including [[polycystic kidney disease]],  drug and toxin-induced chronic tubulointerstitial nephritis and [[reflux nephropathy]] 
* Obstructive such as with bilateral [[kidney stone]]s and diseases of the [[prostate]]

=== Etiology of CRI ===
* '''Glomerular Disease'''
*:* Diagnostic Features
*:*:* [[Red Blood Cell]] (RBC) casts
*:*:* Proteinuria > 3.5 g/d
*:*:* Systemic disease associated with glomerulopathy
*:*:* ''[[Biopsy]]'' often needed for definitive diagnosis of nondiabetic glomerular disease
*:*:* ''Clinical diagnosis'' diabetic nephropathy 
*:*:*:* Suggested by duration of Diabetes Mellitus (DM) 
*:*:*:* (7-8 years type II, 12-15 years type I), 
*:*:*:* Coexistent [[retinopathy]], progressive 
*:*:*:* Nephrotic range [[proteinuria]]
*:* Primary Glomerular Disorders
*:*:* [[Focal glomerulosclerosis]]
*:*:* [[Membranous nephropathy]]
*:*:* [[Membranoproliferative Glomerulonephritis]] (MPGN)
*:* Secondary Glomerular Disorders
*:*:* Diabetic nephropathy 
*:*:* [[Lupus nephritis]]
*:*:* Immunoglobulin A (IgA) nephropathy
*:*:* [[Goodpasture’s syndrome]]
*:*:* [[Amyloidosis]]
* '''Interstitial Disease or Vascular Disease'''
*:* Diagnostic Features:		
*:*:* Bland urinalysis
*:*:* Protein excretion < 2-3 g/d
*:*:* No glomerulopathy-associated systemic disease
*:* Interstitial disorders
*:*:* [[Polycystic kidney disease]] ([[PCKD]])
*:*:* Analgesic abuse
*:*:* Autoimmune disorders ([[sarcoidosis]], [[Sjogren’s]])
*:*:* Vesicoureteral reflux
*:*:* [[Nephrolithiasis]]
*:*:* [[Obstructive uropathy]]
*:* Vascular disorders
*:*:* [[Renal artery stenosis]] (bilateral) 
*:*:* Hypertensive nephrosclerosis (can--chronic insterstitial nephritis)	
*:*:* [[Vasculitis]]
*:*:* [[Scleroderma]]

== Screening / Diagnostic Laboratory Studies==
=== Measurement of Renal Function ===
* Serum creatinine (Cr)
*:* Determined by glomerular filtration rate (GFR) '''and''' by generation, tubular secretion and extrarenal clearance of Cr 
*:* May be inaccurate estimate of function, particularly in patients with mild renal insufficiency
*:* Drugs may inhibit tubular secretion of Cr and falsely elevated serum Cr ([[cimetidine]], [[trimethoprim]] (TMP))
* Creatinine clearance
*:* Estimate:  [(140-age) x body wt (kg)] / [Plasma Cr x 72] (multiply result x 0.85 for women)
*:* Calculated based on 24-hour urine collection
*:*:* CrCl (mL/min) = [Urine Cr (mg/dL) x Urine volume (mL/d)] / [Plasma Cr x 1440]
*:* If [[GFR]] < 50, CrCl overestimates [[GFR]]
*:*:* Calculate 24-hour [[blood urea nitrogen]] ([[BUN]]) clearance (underestimates [[GFR]])
*:*:* Average of [[BUN]] and Cr clearances = GFR

=== Determination of Chronicity ===
* Prior Cr measurements if available
* [[Acute Renal Failure]] (ARF) associated with:
*:* Precipitating factor ([[nephrotoxin]], volume depletion, obstruction)
*:* More symptoms at given level of Cr
*:* Lesser degree of [[anemia]], [[hypocalcemia]], [[hyperphosphatemia]]
* CRI associated with:	
*:* Greater likelihood of hematologic and biochemical abnormalities
*:* Bilateral small [[kidney]]s on [[ultrasound]] (though can be normal in chronic disease)

=== Urinalysis===
*:* May suggest glomerular vs. nonglomerular cause
* [[Urine]] [[sodium]] excretion (FENa):		
*:* More useful for ARF to distinguish prerenal state from acute tubular necrosis (ATN)
*:* May '''not''' be low in volume depleted CRI patient due to tubular dysfunction

=== Ultrasound ===
''' [[Ultrasound]] ''' <br>	
* To rule out obstruction
* To assess kidney size (small = chronic disease; large = DM, amyloidosis)
* Can detect PCKD
* Doppler can evaluate vascular flow – stenosis, thrombosis

=== MRI and CT ===
''' [[CT scan]] '''<br>	
* If [[nephrolithiasis]] suspected (best test) – can detect radiolucent stones
* More sensitive than ultrasound for PCKD
* Best evaluation for cysts/malignancy

==== Other Imaging Findings ====

* [[Kidney]], [[Ureter]], and [[Bladder]] (KUB)  	
*:* If [[nephrolithiasis]] suspected (screening test)
*:*:* Will detect calcium-containing, struvite, and cystine stones
*:*:* Will miss uric acid stones, small stones, and stones overlying bony structures

=== Other Diagnostic Studies ===

===== Biopsy =====
* Indications for Biopsy	
*:* Isolated glomerular hematuria with proteinuria
*:* [[Nephrotic syndrome]]
*:* [[Acute nephritic syndrome]]
*:* Unexplained acute or subacute renal failure
* Contraindications	
*:* Uncorrectable bleeding disorder
*:* Small kidneys indicative of chronic, irreversibile disease (<7-8 cm length)
*:* Severe hypertension not controllable with medications
*:* Multiple, bilateral cysts or a renal tumor
*:* [[Hydronephrosis]]
*:* Active renal or perirenal infection
*:* Solitary native kidney (relative contraindication)

==Treatment==
The goal of therapy is to slow down or halt the otherwise relentless progression of CRF to ESRD. Control of [[blood pressure]] and treatment of the original disease, whenever feasible, are the broad principles of management. Generally, [[angiotensin converting enzyme inhibitor]]s (ACEIs) or angiotensin II receptor antagonists (ARBs) are used, as they have been found to slow the progression to ESRD.<ref>Ruggenenti P, Perna A, Gherardi G, Gaspari F, Benini R, Remuzzi G. Renal function and requirement for dialysis in chronic nephropathy patients on long-term ramipril: REIN follow-up trial. Gruppo Italiano di Studi Epidemiologici in Nefrologia (GISEN). Ramipril Efficacy in Nephropathy. Lancet. 1998 Oct 17;352(9136):1252-6. PMID 9788454.</ref><ref>Ruggenenti P, Perna A, Gherardi G, Garini G, Zoccali C, Salvadori M, Scolari F, Schena FP, Remuzzi G. Renoprotective properties of ACE-inhibition in non-diabetic nephropathies with non-nephrotic proteinuria. Lancet. 1999 Jul 31;354(9176):359-64. PMID 10437863.</ref>

Replacement of [[erythropoietin]] and [[vitamin D3]], two hormones processed by the kidney, is usually necessary, as is [[calcium]].  [[Phosphate binders]] are used to control the serum [[phosphate]] levels, which are usually elevated in chronic renal failure.

After ESRD occurs, renal replacement therapy is required, in the form of either [[dialysis]] or a [[Kidney_transplant|transplant]].

* '''Treatment of Reversible Exacerbants'''
*:* Volume Depletion	
*:*:* May be subtle
*:*:* Autoregulation impaired with [[DM]], [[hypertension]], CRI--decreases GFR with mild volume depletion 
*:*:* Careful trial of volume repletion may--return of baseline renal function 
*:*:* (Increase dietary Na, reduce diuretic dosing)
*:* [[Nephrotoxin]]s		
*:*:* NSAIDs 	
*:*:*:* Most toxic in setting of volume depletion, CHF, diuretic use
*:*:*:* Reduce [[prostaglandin]] (PG) synthesis--unopposed vasoconstriction with decreased GFR
*:*:*:* Can also cause ATN ([[acute tubular necrosis]])
*:*:* [[Aminoglycoside]]s 
*:*:*:* Nonoliguric ARF typically occurs at 7-10 days 
*:*:*:* Increased risk with older patients, prolonged therapy and greater total dose
*:*:* IV contrast 	
*:*:*:* ARF usually occurs within 24-48 hours of dye administration
*:*:*:* Peak Cr after 5-7 days with return to baseline at 10-14 days
*:*:*:* Risk ARF increased with DM and higher volume of dye
*:*:* Note: certain meds increase serum Cr (via inhibiting Cr secretion or interfering with assay) without changing GFR, e.g. cimetidine, trimethoprim (TMP), cefoxitin, flucytosine; BUN will not rise because GFR is preserved
*:* Urinary Tract Obstruction	
*:*:* Most commonly due to prostatic hypertrophy in men 
*:*:* Other causes:  
*:*:*:* [[Nephrolithiasis]] 
*:*:*:* [[Tumor]]
*:*:*:* [[Neurogenic bladder]]
*:*:* Results in reduced [[GFR]] and impaired tubular function
*:*:* Consider ultrasound, urologic evaluation
* '''Reduce Progression'''
*:* Protective therapy most effective if initiated '''early''', before Cr > 1.5-2.0 mg/dL 
*:* Treat [[Hypertension]]	
*:*:* Systemic [[hypertension]]--elevated intraglomerular pressure +/or glom hypertrophy
*:*:* Blood Pressue (BP) control shown in multiple trials to slow progression of renal disease
*:*:* Goal BP < 130/80-85; < 125/75 in patients with proteinuria > 1-2 g/d
*:*:* ACE inhibitors (ACEI) and Angiotensin II receptor blockers (ARB) preferred 1st line agents due to renoprotective effects
*:*:* Additional agents as needed, including diuretics if volume overload
*:* Restrict Dietary Protein
*:*:* Controversial – may decrease intraglomerular pressure
*:*:* Conflicting studies – some show benefit, others do not
*:*:* No significant adverse effects shown in large trial
*:*:* Recommendations 
*:*:*:* No restriction (> 0.8 g/kg/d) if GFR 25-55 mL/min
*:*:*:* Limit protein to 0.8 g/kg/d if progression or uremic symptoms
*:*:*:* Limit to 0.6 g/kg/d if severe CRI (GFR 13-25 mL/min)
*:*:* Close follow-up by dietician given risk of malnutrition in CRI population
*:* Control blood sugar:	
*:*:* Tight control (A1c < 7.0, FBS 70-120) reduces progression in DM I
*:*:* Unclear if as beneficial in DM II, but potentially helpful
* '''Treat complications'''
*:* Volume Overload		
*:*:* Impaired excretion of Na/H2O due to decreased GFR +/- AII/aldo activation
*:*:* Restrict dietary Na to 1-2 g/d if hypertension or edema
*:*:* [[Diuretic]]s		
*:*:*:* [[Thiazide]]s ineffective if [[GFR]] < 25 mL/min (~ Cr > 2-3)
*:*:*:* Switch to loop diuretic as Cr rises; may need bid dosing
*:*:*:* Addition of [[thiazide]] to loop diuretic can--additional diuresis
*:*:*:* Watch for excessive volume depletion
*:* [[Hyperkalemia]]		
*:*:* K usually maintained until GFR < 15-20 mL/min
*:*:* Increased risk of [[hyperkalemia]] with oliguria, high [[K]] diet, ([[ACEI]] therapy)
*:*:* Increased risk with many meds:  [[ACEI]], [[NSAID]]s, K-sparing diuretics, [[digoxin]], [[TMP]]
*:*:* Increased risk in diabetics with type IV RTA
*:*:* Management
*:*:*:* Low K diet (< 60 mEq/d) once GFR < 15 mL/min
*:*:*:* Avoidance of salt substitutes (may contain K salts)
*:*:*:* +/- [[loop diuretic]]
*:*:*:* Low dose Kayexelate (5 g with meals) if needed 
*:* Ca/PO4 Abnormalities	
*:*:* Reduced renal synthesis 1,25-(OH)2D--low serum Ca-- 2° [[hyperparathyroidism]]
*:*:*:* (Occurs when [[GFR]] < 40 mL/min)
*:*:* Reduced [[GFR]]--phosphate retention 
*:*:* Elevated [[parathyroid hormone]] ([[PTH]])--mobilization of Ca from bone; increased excretion PO4
*:*:*:* Allows maintenance of normal Ca/PO4 while GFR > 30 mL/min
*:*:*:* Causes [[renal osteodystrophy]]
*:*:*:* Once [[GFR]] < 25-30 mL/min, [[hyperphosphatemia]] occurs
*:*:* Therapy goals = normalize Ca/PO4 and maintain [[parathyroid hormone]] (PTH)< 200 (2-3x uln)
*:*:*:* Ca/PO4 management should be initiated when Cr ~ 2 
*:*:*:* CaxPO4 product should be < 60 to prevent met calcification
*:*:*:* Low PO4 diet:  < 800 mg/d (challenging)
*:*:*:* Ca-based oral PO4 binders:  Ca acetate or CaCO3 with meals
*:*:*:* Avoid Al-based PO4 binders except for acute therapy of hi CaxPO4 products
*:*:*:*:* (Al toxicity = [[osteomalacia]], [[anemia]], [[encephalopathy]])
*:*:*:* Avoid Ca citrate (increases gastrointestinal absorption of aluminum)
*:*:*:* RenaGel = new non-Ca/Al-containing PO4 binder (cationic polymer) 
*:*:*:*:* (For patients who cannot tolerate CaCO3 or need additional agent)
*:*:*:* [[Calcitriol]] 0.125-0.25 mg/d improves Ca & PTH levels, decreases bone disease
*:*:*:*:* (Monitor Ca--reduce dose if hyercalcemic)
*:* [[Metabolic Acidosis]]	
*:*:* Occurs when [[GFR]] < 25 mL/min due to inability to excrete H+ ions
*:*:* Underlying cause = impaired renal NH3 prodxn and HCO3 reabsorption
*:*:* Risk = bone buffering of acidosis--worsened osteodystrophy via Ca/PO4 loss
*:*:*:* Increased skeletal muscle breakdown--loss of lean body mass
*:*:* Therapy goal = HCO3 > 22 mEq/L via alkali therapy (NaHCO3 0.5-1 mEq/kg/d)	
*:* [[Anemia]]
*:*:* Normocytic, normochromic, hypoproliferative anemia due to reduced erythropoietin production
*:*:* May be exacerbated by reduced rbc survival, coexistent Fe/folate deficiency, etc.
*:*:* Generally occurs when Cr > 2-3 mg/dL
*:*:* If untreated, [[hematocrit]] (Hct) usually stabilizes at ~ 25
*:*:* Therapy recommendations = erythropoietin if symptomatic anemia or Hgb < 10 g/dL (in pre-dialysis patients)
*:*:*:* Goal Hct 33-36
*:*:*:* Must replete Fe stores first (oral FeSO4)
*:*:*:* Initial dose ~ 150 U/kg sc weekly to increase Hct
*:*:*:* Maintenance dose ~ 75 U/kg weekly once Hct goal reached
*:*:*:* Improves symtoms and may reduce left ventricle (LV) mass (via improvemt of hyperdynamic state)
*:*:*:* Side effects = increased blood pressure (BP); may need to augment antihypertensive regimen
* '''Plan for Renal Replacement Therapy (RRT)'''
*:* Indications for Dialysis	
*:*:* [[Malnutrition]]
*:*:* CrCl M 10-15 mL/min
*:*:* Symptoms of [[uremia]] related complications  ([[pericarditis]], [[encephalopathy]])
*:*:* [[Hyperkalemia]], acidosis not responsive to medical therapy
*:*:* Volume overload / [[CHF]]
*:* RRT modalities
*:*:* [[Hemodialysis]]
*:*:* [[Peritoneal dialysis]]
*:*:* [[Renal transplant]]
*:* Access for [[hemodialysis]] should be established when [[GFR]] < 25 mL/min (estimated ESRD within 1 year)
*:* Diabetics tend to require dialysis sooner than non-diabetics because more symptomatic at given [[GFR]]
* Indications for referral to nephrologist
*:* Unclear etiology of new or chronic [[renal insufficiency]] 
*:* For diagnostic evaluation, e.g. [[biopsy]]
*:* [[GFR]] < 50 mL/min:  i.e. '''before''' vascular access/RRT required

==Prognosis==
The prognosis of patients with [[chronic kidney disease]] is guarded as [[epidemiology|epidemiological data]] has shown that all cause [[death|mortality]] (the overall death rate) increases as kidney function decreases.<ref name=perazella16538076>Perazella MA, Khan S. Increased mortality in chronic kidney disease: a call to action. Am J Med Sci. 2006 Mar;331(3):150-3. PMID 16538076.</ref>  The leading cause of death in patients with chronic kidney disease is cardiovascular disease, regardless of whether there is progression to ESRD.<ref name=perazella16538076/><ref>Sarnak MJ, Levey AS, Schoolwerth AC, Coresh J, Culleton B, Hamm LL, McCullough PA, Kasiske BL, Kelepouris E, Klag MJ, Parfrey P, Pfeffer M, Raij L, Spinosa DJ, Wilson PW; American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention. Kidney disease as a risk factor for development of cardiovascular disease: a statement from the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention. Circulation. 2003 Oct 28;108(17):2154-69. PMID 14581387. [http://circ.ahajournals.org/cgi/content/full/108/17/2154 Free Full Text].</ref><ref>Tonelli M, Wiebe N, Culleton B, House A, Rabbat C, Fok M, McAlister F, Garg AX. Chronic Kidney Disease and Mortality Risk: A Systematic Review. J Am Soc Nephrol. 2006 May 31; PMID 16738019.</ref>

While renal replacement therapies can maintain patients indefinitely and prolong life, the quality of life is severely affected.<ref>Heidenheim AP, Kooistra MP, Lindsay RM. Quality of life. Contrib Nephrol. 2004;145:99-105. PMID 15496796.</ref><ref>de Francisco AL, Pinera C. Challenges and future of renal replacement therapy. Hemodial Int. 2006 Jan;10 Suppl 1:S19-23. PMID 16441862.</ref> [[Renal transplantation]] increases the survival of patients with ESRD significantly when compared to other therapeutic options;<ref>Groothoff JW. Long-term outcomes of children with end-stage renal disease. Pediatr Nephrol. 2005 Jul;20(7):849-53. Epub 2005 Apr 15. PMID 15834618.</ref><ref>Giri M. Choice of renal replacement therapy in patients with diabetic end stage renal disease. EDTNA ERCA J. 2004 Jul-Sep;30(3):138-42. PMID 15715116.</ref> however, it is associated with an increased short-term mortality (due to complications of the surgery). Transplantation aside, high intensity [[home hemodialysis]] appears to be associated with improved survival and a greater quality of life, when compared to the conventional thrice weekly [[hemodialysis]] and [[peritoneal dialysis]].<ref>Pierratos A, McFarlane P, Chan CT. Quotidian dialysis--update 2005. Curr Opin Nephrol Hypertens. 2005 Mar;14(2):119-24. PMID 15687837.</ref>

==See also==
*[[Acute renal failure]]
*[[Dialysis]]
*[[Hepatorenal syndrome]]
*[[Renal failure]]
*[[Artificial kidney]]

==References==
{{reflist|2}}

==External links==

*[http://www.kidney.org/ National Kidney Foundation]
*[http://www.emedicine.com/emerg/topic501.htm Renal Failure, Chronic and Dialysis Complications] - emedicine.com
*[http://www.emedicine.com/med/topic374.htm Chronic Renal Failure] - emedicine.com
<br>

{{Nephrology}}

{{SIB}}

[[Category:Kidney diseases]]
[[Category:Organ failure]]
[[Category:Nephrology]]

[[de:Chronisches Nierenversagen]]
[[es:Insuficiencia renal crónica]]
[[id:Gagal ginjal kronis]]
[[it:Insufficienza renale]]
[[ja:慢性腎不全]]
[[pt:Insuficiência renal crônica]]
[[ru:Хроническая почечная недостаточность]]
[[sv:Kronisk njursvikt]]


{{WikiDoc Help Menu}}
{{WikiDoc Sources}}