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JN ( 2010; :04) 399-40723EPHROL

INTRODUCTION

Demands on nephrology services are growing. There were32,406 Canadians with end-stage kidney disease (ESKD)in 2005, compared with 18,000 in 1996, an average annualgrowth rate of 6.6% (1, 2). Patients with ESKD represent onlyabout 2% of all patients with chronic kidney disease (CKD)(3), implying there were 1.6 million Canadians with CKD in2005. Many of these are cared for by primary care physi-cians, but many are followed by a nephrologist or a multidis-ciplinary team. In 2008, there were 491 nephrologists prac-ticing in Canada (4), compared with 332 in 1998 (5).While patients with CKD comprise a substantial portionof the patients that nephrologists deal with, one must

A BSTRACT

Introduction: Referrals to nephrologists comprise notonly patients with chronic kidney disease but alsothose with other nephrological conditions. There maybe confusion about when to refer a patient to a neph-rologist. We conducted a literature review to identifypreexisting priority-setting, triage or referral criteriadeveloped to guide referrals from primary care to anephrologist.

Methods: Medline and Cochrane databases weresearched (1997 to 2008) using search terms: referral,consultation, triage and a list of specied nephrologi-cal conditions. Abstracts were assessed by 2 review-ers using criteria to determine relevance. Citation andhand searches were done on papers selected for re-view; relevant Web sites were also consulted. Two re-viewers read all selected papers to determine if theymet the objectives. One reviewer abstracted relevantdata from each retained reference and compiled theresults into a report, which was reviewed by 3 practic-ing nephrologists.

Results: There were 18 retained papers, reports orWeb sites; 4 of these were professional national guide-lines. All but 1 reference cited serum creatinine or esti-mated glomerular ltration rate as a criterion for refer-ral. Other referral criteria were proteinuria (8 sources),blood pressure (5 sources), electrolytes (3 sources) orhematuria (3 sources). There was inconsistency in re-ferral recommendations.

1 Strategy & Performance, Alberta Health Services, Alberta - Canada

2 Department of Community Health Sciences, Facultyof Medicine, University of Calgary, Calgary, Alberta -Canada

3 Department of Medicine, Faculty of Medicine,University of Calgary, Calgary, Alberta - Canada

Carolyn De Coster 1,2 , Kevin McLaughlin 3,Tom W. Noseworthy 2

Criteria for referring patients with renaldisease for nephrology consultation: a reviewof the literature

REVIEW

Conclusions: The differing advice identied in theliterature results in confusion as to when patientsshould be referred to a nephrologist. Nephrologists,an already strained human resource, must prioritizerequests for consultation using an undened and nodoubt inconsistent metric. Standardized, diagnosis-neutral criteria would benet both primary care pro-viders and nephrologists.

Key words: Consultation, Glomerular ltration rate, Kid- ney diseases, Nephrology, Referral, Review


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remember that the scope of practice includes a varietyof other nephrological conditions as well, such as acuteinfectious or inammatory renal diseases, benign and ma-lignant tumors, recurring urolithiasis, electrolyte abnor-malities, hemodynamic imbalances and refractory hyper-tension (6). In addition, some systemic diseases such asthe vasculitides or lupus erythematosus may have renalmanifestations.Not all patients with CKD will progress to ESKD; however,for those who will progress, earlier referral leads to im-proved outcomes (3, 5, 7, 8). Many patients can and shouldbe managed by their primary care providers, but there maybe uncertainty about when to refer. We conducted a litera-ture review to assess whether there were uniform criteriato guide referrals from primary care to specialist care/con-sultation usually provided by a nephrologist. Furthermorewe were interested to know if there were different levels ofurgency or priority in referral criteria. This paper describesthe ndings of the review.

M ETHODS

The methods used were similar to standard methods usedin systematic reviews, with some modications (9-11). Weallowed for the fact that we might uncover guidelines forprioritizing referrals used by individual facilities on Web sitesor in letters to the editor. Therefore, we erred on the sideof inclusiveness and followed up any papers that seemedpotentially relevant, regardless of quality.We searched Medline and Cochrane databases from 1997to 2008, English only, using the terms referral, triage or con-

sultation AND at least 1 from a list of nephrology-specicsearch terms (Appendix). The list had been reviewed by anephrologist and family physician and included terms suchas glomerulonephritis, diabetic nephropathies, polycystic

kidney diseases, proteinuria, renal dialysis, elevated BUN and Alport syndrome. The search yielded 655 abstractsand titles (Fig. 1).Criteria for the selection of relevant abstracts were devel-oped, tested and revised in an iterative process. All ab-stracts were reviewed by 2 reviewers and rated as Yes (Y),No (N) or possible (Q). Papers rated as Y/Q, Q/Q or Y/Nwere reviewed by a third reviewer. At the end of this pro-cess, 65 papers had been identied for retrieval. The crite-ria for inclusion/exclusion were revised further, and the 65abstracts were assessed again by 3 reviewers. Twenty-fourpapers were subsequently retrieved and read in full by 2 re-viewers; 13 of these papers were retained. Citation search-es and manual reference list searches were also conductedon papers that were selected. As well relevant Web sites

Fig. 1 - Diagram of literature search and retention strategy fornephrology referral review.

were consulted, including those of the Canadian Society ofNephrology; Kidney Disease: Improving Global Outcomes;Caring for Australians with Renal Impairment; EuropeanBest Practice Guidelines; and the Renal Association (UK).Five more citations were identied and retained. One re-viewer abstracted the relevant data from each retained ref-erence and compiled the results. The resulting report wasthen reviewed by 3 practising nephrologists.

R ESULTS

Table I identies the 18 retained papers, reports or Websites (3, 5, 7, 8, 12-24). Four of the identied citations areprofessional national guidelines from Canada (18), theUnited States (16), the United Kingdom (15) or Australia(21). The largest number of citations were from the UnitedStates (8 citations), followed by Canada (4 citations), theUnited Kingdom (3 citations), other European countries (2citations) and Australia (1 citation). Almost all of the crite-ria for referral included mention of either serum creatinineor estimated glomerular ltration rate (eGFR). Criteria thatwere sometimes, but not universally, included were mea-sure of proteinuria (8 sources), blood pressure (5 sources),electrolytes (3 sources) or hematuria (3 sources). Othercriteria were anemia, presence of diabetes, the need for arenal biopsy, problems with management or primary careprovider concern.


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TABLE ISOURCES FOR CRITERIA FOR REFERRAL TO NEPHROLOGY

Author, source, year Country GFR ↓ or SeCR ↑ Proteinuria Electrolytes Hematuria BP Other

Bakris. Postgrad Med 2003 (12) US • •

Burden and Tomson. Clin Med 2005 (13)* UK • • • • • •

Canadian Society of Nephrology. CanFam Physician 2000 (7)

Canada •

Crooks. Southern California KaiserPermanente (PowerPoint presentation)2005**

US • • • •

Jenkins et al. Nurs Times 2007 (14)* UK • • • • • •

Joint Specialty Committee on RenalMedicine of Royal College of Physicians& the Renal Association & the RoyalCollege of General Practitioners. RoyalCollege of Physicians 2006 (15)

UK • • • • • •

National Kidney Foundation: Kidney Dis-ease Outcomes Quality Initiative (KDOQI)Web site 2002 (16)

US •

Levin. Nephrol Dial Transplant 2001 (17) Canada •

Levin and Mendelssohn. CanadianSociety of Nephrology 2006 (18)

Canada • • •

Mendelssohn et al. CMAJ 1999 (5) Canada •

Obrador and Pereira. Am J Kidney Dis1998 (8)

US •

Schwartz and Textor. Mayo Clin Proc2006 (19)

US •

Snyder and Pendergraph. Am Fam Phy-sician 2005 (20)

US • •

St Peter et al. Am J Kidney Dis 2003 (3) US •

Thomas. Nephrology 2007 (21) Australia • • • •

Thorp and Eastman, Am J Manag Care

2004 (22)US •

Van Biesen et al. Nephrol Dial Transplant2006 (23)

Belgium •

Wauters et al. Nephrol Dial Transplant2005 (24)

Switzerland,Belgium, UK,

Germany

• •

Dots indicate that this criterion was included in the reference cited.BP = blood pressure; GFR ↓ = decrease in glomerular ltration rate; ↑ SeCR = increase in serum creatinine.*Referenced the UK Joint Specialty Guidelines.**Crooks P. GFR implementation & CKD program at Southern California Kaiser Permanente. October 4, 2005 [powerpoint presentation].


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TABLE IISPECIFIC RECOMMENDATIONS FOR REFERRAL OF PATIENTS WITH REDUCED KIDNEY FUNCTION, EXCLUDING

ACUTE RENAL FAILURE

Author, year Note GFR ↓ or SeCR ↑ ProteinuriaElectrolytes,hematuria, BP

Other

Bakris, 2003 (12) Referral fordiabetics withdiabeticnephropathy

SeCr 1.5 mg/dL Threefold-to-fourfold increasein albuminuria in 6monthsCannot reducealbuminuria by30% with good BPcontrol

Burden and Tomson,2005 (13)

See Royal College(UK) 2006

Canadian Society ofNephrology, 2000 (7)

Establishedprogressivelyincreasing SeCr ORSeCr ≥ 300 µmol/L

Crooks, 2005 eGFR 1,000 mg/day Hypertension hardto manage

SuspectedEPO-deciencyanemia

Jenkins et al, 2007(14)

See Royal College(UK) 2006

Royal College (UK),2006 (15)

eGFR 45mg/mmolProteinuria withedema and lowserum albumin*Proteinuria + he-maturiaDiabetes w.increasing protei-nuria

K+ ≥ 6-7 mmol/L*Malignanthypertension*

Abnormal K +, Ca 2+ ,PO 3-

BP >150/90 on 3agentsMicroscopichematuriaUnexplained mac-roscopic hematuria

Suspectedsystemic illness,e.g., SLE*Unexplainedanemia(Hgb 70 ng/L(7.7 pmol/L)

KDOQI, 2002 (16) eGFR 60mg/mmol

Progressive lossof kidneyfunctionProblems w.managementof BP, meds orother

to be continued


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Author, year Note GFR ↓ or SeCR ↑ ProteinuriaElectrolytes,hematuria, BP

Other

Mendelssohn et al,1999 (5)

SeCr 300 µmol/L

Obrador and Pereira,1998 (8)

SeCr 1.5 mg/dL inwomen or 2.0 mg/dLin men

Schwartz and Textor,2006 (19)

Editorial eGFR


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Proteinuria is a hallmark of many renal disorders (26). Con-sequently, several sources cited proteinuria or albuminuriaas a criterion for referral. The UK guidelines recommendreferral when the protein to creatinine ratio (PCR) is morethan 45 mg/mmol, which is equivalent to an albumin to cre-atinine ratio (ACR) of more than 30 mg/mmol or a urinaryprotein excretion of about 0.5 g/24 hours (15). The UK val-ues are lower than those recommended by the CanadianSociety of Nephrology; it advises referral with persistentdipstick proteinuria, PCR >100 mg/mmol or ACR >60 mg/ mmol. The Canadian values are similar to those recom-mended by Crooks (United States) and Thomas (Austra-lia) (21) who used protein excretion of more than 1 g in 24hours to dene proteinuria that should be referred.Diabetes is a leading cause of CKD. It is estimated that40% of all diabetics in the United States have CKD, com-pared with 15% of nondiabetics, and Canadian estimatesare that 35% of new ESKD patients have diabetes as theprimary cause (27, 28). Three sources suggested that dia-betic patients be referred based on proteinuria: Bakris ad-vised referral when there had been a threefold-to-fourfoldincrease in albuminuria in 6 months or an inability to re-duce albuminuria by 30% even with effective control ofhypertension (12); Wauters et al suggested referral withestablished microalbuminuria (24) and the UK guidelinesrecommended referral when proteinuria is increasing. Mi-croalbuminuria may be dened as 30 to 300 mg urinaryalbumin per 24 hours, whereas macroalbuminuria is morethan 300 mg urinary albumin per 24 hours (29).Only the UK guidelines made specic reference to elec-trolytes as a reason for referral, stating that a serum po-tassium above 7.0 mmol/L required an emergency con-sultation with a nephrologist, serum potassium between6.0 and 7.0 mmol/L required an urgent consultation andelevated levels of potassium, calcium or phosphate in astage 3 CKD patient requires routine referral. Hematuriawas also mentioned only in the UK guidelines. Refractoryhypertension was identied in 4 sources (15, 18, 21). TheUK guidelines were the most specic, advising emergencyreferral for malignant hypertension and routine referral forrefractory hypertension, dened as blood pressure (BP) of150/90 mm Hg despite therapy with 3 drugs from differentclasses. Anemia as a reason for referral was identied by3 sources (15, 21).

D ISCUSSION

Our review demonstrated that there is a lack of consistencyin referral recommendations, and furthermore, that manyguidelines mention only eGFR or serum creatinine as a refer-

ral criterion. The UK guidelines provided the most compre-hensive description of when patients should be referred andincluded 3 urgency bands (15). These guidelines describednot only absolute values of eGFR, but also a change in eGFRthat should prompt referral. Other criteria included protei-nuria, electrolytes, hypertension, hematuria, parathyroidhormone, anemia and systemic illness. They also outline thetypes of patients who can be managed by the primary careprovider, possibly with advice from a nephrologist. No othersources included that level of detail. The Australian guide-lines cite eGFR, proteinuria, hypertension, anemia and co-morbid illness (21). The Canadian guidelines include eGFR,proteinuria and problems with management of hypertension,medications or other issues (18). These 3 guidelines are themost detailed, whereas several other sources focused onlyon eGFR or serum creatinine as the criterion for referral (3,8, 16, 19, 22, 23). It is worth noting that different recalcula-tion methods can yield eGFR results varying by as much as85% (23).Sources conict on whether referral should occur at CKDstage 3 (3, 13, 21) or stage 4 (7, 22, 25). Earlier referralhas the potential to improve the outcomes of comorbid dis-eases; decrease the number of complications such as ane-mia, cardiovascular disease, diabetes, hypertension andmalnutrition; delay the onset of end-stage kidney disease;improve patient survival; reduce the use of temporary vas-cular access devices; optimize the patient’s biochemical,physical and psychological state for the initiation of dialysis;improve vocational outcomes and reduce hospital stays (3,5, 7, 8). The differential impact on nephrologists betweenreferral at CKD stage 3 or 4 is quite substantial; St. Peter etal reported that 39% of patients with CKD are in stage 3,whereas only 2% are in stage 4, or 700,000 versus 64,000patients, using 2005 estimates of CKD in Canada (3). TheCanadian Society of Nephrology recommends referral atstage 4 (7, 25). Two sources also stated that a decrease inGFR of 15% (15) or 20% (30) should prompt referral.While earlier referral has been recommended for improvedoutcomes, earlier referral coupled with longer survival ofpatients may overwhelm nephrological services (3, 7, 23).Therefore joint management of patients with CKD has beensuggested (3, 7, 17, 18, 20, 22). Multidisciplinary renal teamscan provide patients with better information and education,monitoring and follow-up, and also create opportunities fordiscussion groups and contacts with other ESKD patients(31). A survey found that most Canadian nephrologists uti-lize such clinics routinely (32). While the majority of patientswere referred when they are in CKD stage 4, two thirds ofnephrologists surveyed said they would prefer referral whilepatients were still in stage 3 (32).


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Wauters et al proposed a timetable for sharing the care ofCKD patients, progressing from a single consultation to es-tablish a diagnosis and suggest a follow-up plan, to annualappointments with the nephrologist once CKD has been di-agnosed but does not progress to ESKD, to management ofthe patient once GFR is


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Kidney stonesKidney transplantationKidney tubular necrosisKidney(s)Light chain cast nephropathyLupus nephritisMembranous nephropathyMembranoproliferative glomerulonephritisMesangioproliferativeMesoblastic nephromaMicroalbuminuriaMicroscopic polyangiitisMinimal change diseaseMultiple myelomaNephritic syndrome

NephritisNephrocalcinosisNephrolithiasisNephrologist(s)NephrologyNephropathyNephrosclerosisNephrosisNephrotic syndromePaediatric nephrologyPainful bladder syndromePancreas transplantationPediatric nephrologyPerinephritisPeritoneal dialysisPolycystic kidneyPolycystic kidney diseasesPost infectious glomerulonephritisProstate enlargementProstatitisProteinuriaPyelitis

PyelocystitisPyelonephritisRenalRenal artery obstructionRenal artery stenosisRenal cell carcinomaRenal cystic disordersRenal diabetesRenal dialysisRenal diseases/disordersRenal failureRenal insufciencyRenal replacement therapyRenal transplantationRenal tuberculosis

Thin basement membrane diseaseUremiaUrinary tract infectionsWegener granulomatosisWilms tumorWolfram syndrome

Financial support: This work was funded by Alberta Health andWellness – Access to Medical Services Grant.

Conict of interest statement: None of the authors has a nancial

or other relationship that might lead to a conict of interest withrespect to the research.

Address for correspondence:Carolyn De Coster, PhD, RNSenior Researcher

Alberta Health Services4520 – 16th Avenue NWCalgary, Alberta T3B 0M6, [email protected]

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Received: July 30, 2009 Accepted: August 05, 2009

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